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Cell stress inflames the gut: New insights into chronic bowel inflammation

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Posted 7/3/2014 12:20 AM (GMT 0)
FT's haven't been known to do so well in IBD, especially long term, but very little short term either. I don't really know what the mucus barrier situation is in C-Diff patients where there is much evidence that FT's do work.
Posted 7/3/2014 1:30 AM (GMT 0)
@maurader

Of course it's up-regulated as a result of ER stress... and was previously thought to just be involved in the eventual apoptotic response initiated to eliminate (kill) cells. It also appears to be involved in inflammatory pathway delaying healing.

The two (ER stress and the induction of CHOP) are a close relationship.

It is also known to be up-regulated in those with IBD...................... You'll just have to look around perhaps.
Posted 7/3/2014 2:04 AM (GMT 0)
Conquer, because mucus isnt the freaking problem it is a symptom.


Maurauder.. it is pointless to argue with CM.. He doesnt believe in some science, has super interesting interpretations of other parts....He pulls crap out of his ass and then will attack you personally if you disagree. Ive been browsing not logged in with my safey safe ignore list so I got sucked into this thread because of OM..


I feel like you are smart OM and you post good things sometimes.. you can sometimes get on great tangents ;)...but ugh, your side kick choice prevents me from really speaking to you most threads. You are so quick to disagree with what Im saying.. its not soaps its.. yadda yadda yadda.. you guys regurgitate so much stuff but rarely can you connect the dots.. and if anyone spends their time trying to help it ends up like this...

Oy vey, learn from my wasted time Maurauder.

Post Edited (PathogenKiller) : 7/2/2014 8:11:03 PM (GMT-6)

Posted 7/3/2014 4:42 AM (GMT 0)

Canada Mark said...
@maurader

Of course it's up-regulated as a result of ER stress... and was previously thought to just be involved in the eventual apoptotic response initiated to eliminate (kill) cells. It also appears to be involved in inflammatory pathway delaying healing.

The two (ER stress and the induction of CHOP) are a close relationship.

It is also known to be up-regulated in those with IBD...................... You'll just have to look around perhaps.

Yes Im not arguing against the fact that ER stress --> CHOP activation. But just because such a situation CAN occur, doesnt mean it DOES. This happens all the time in the body. So just because ER stress occurs in IBD, doesnt mean necessarily that CHOP up-regulation occurs. Other things regulate CHOP expression, not just ER stress, and those other factors can influence its expression pattern in IBD.

My point is that the papers that are cited for this fact dont even mention CHOP, so I dont think we can say for sure that CHOP is up-regulated since the one paper that looks at CHOP specifically shows its DOWN-regulated. Do you see what Im saying at least? Can you show me a paper that actually looks at CHOP expression IN THE CONTEXT OF IBD specifically, not in the context of induction of ER stress? Thats what Im getting at : )

@PathogenKiller - I cant speak to your comments as Ive had very pleasant interactions with both of them so far. Besides, science is all about debating the data, so I enjoy this very much. Leads to further understanding and more research. Ya Im a science nerd : p
Posted 7/3/2014 5:08 AM (GMT 0)
@pathogenkiller: the mucous could very well be a symptom and thats what part of the debate is about. It could be, as mentioned in the paper that CM posted, that interaction with certain bacteria stimulates the colon to produce a more "firm" mucous layer.

But i personally don't think thats the whole story. Otherwise why would people who get into long long remissions on FTs get flareups again? Sure maybe because they used antibiotics/emulsifiers etc but so does everybody. Why is it that we have such a propensity to let the bad bugs proliferate and then degrade our mucous?
Posted 7/3/2014 7:47 AM (GMT 0)
@Path - I'm not arguing anything - or at least I don't think I am. You seem to be though...

--------
@marauder

Again, as I mentioned before I think the paper you're referring to showing it down-regulted is specific to bacterial and T-cell mediated colitis...... but actually upregulated in Ulcerative Coltis. So that's causing the first bit of confusion. It's a wording thing. There's a difference between Bacterial Colitis/T-cell mediated colts and actual Ulcerative Colits and that statement is pointing this out and showing down and up regulation respectively.

-------
In regards to the other two papers:

CHOP transcription factors such as C/EBPb & C/EPBa fall downstream under signalling from the IL-17 receptor. IL-17 is a cytokine. When IL-17 binds to it's receptor it sets off a chain of events. This chain of events or molecular signalling ultimately results in NF-kB activation which results in cytokine expression and it also recruits components of the MAP kinase pathway and this results in in enhancing the stability of cytokine mRNA. So again there's a big chain of events... Like anything involving the immune system it's confusing as heck at first and ongoing!

Now - activation of the C/EBP family transcription factors (Transcription factors are proteins and they control DNA to mRNA translation so ultimately they help build specific molecules to respond/induce something) - anyway C/EPB family transcription factors IN ADDITION to up-regulation of NF-kB and members of the MAP kinase pathway, signalling through IL-17RA and IL-17RC proteins has also been shown to activate the transcription factors C/EPBa and C/EPBb, which promote expression of IL-6, one of the quintessential inflammatory cytokines.

So here's the deal: Cytokines (Like IL17 and IL-6 etc) are molecules that communicate among the cells of the immune system. So they basically say or instruct what to do - and ultimately they can instruct a cell when to survive and when to die. We hear a ton about all these in IBD on this site.

Now, getting to the point here - there are loops... much like with toll like receptors. These loops are there to keep check or keep things from spiralling out of control like aberrant cell death or inflammation and such. These loops are controlled by transcription regulation. What the other papers are referring to is the transcription regulators - and this in turn effects CHOP expression and seem to be indicating an increase in this (and other things) in IBD - though they may not mention CHOP directly because they are looking at transcription regulation in bulk.

Also bear in mind IL-6 and IL-17 are often (if not always) detected IBD whereas not in normal controls.

------
At the end of the day - often things go down these crazy immune paths and lead nowhere in relation to IBD except another "way" or route that is a "possible" step that "may" have gone wrong... sorta thing. So I wouldn't spend to much time focusing on it unless it's out of sheer interest or curiosity, which is pretty cool anyway to have a curiosity about things. Who know's what you might stumble upon or think of etc. Perhaps start with noting the genes that regulate transcription factors and work forward from there.

Sorry, source for all of the above - Page 129 Chapter 4 Kirby Immunology Seventh Edition. Might be a good start as well.

I'll take some time not tomorrow but perhaps the ext day or so and maybe search in more detail. I should have some older stuff bookmarked away on here.

Side not - I think (but not sure) that unfolded protein response is implicated in a lot of autoimmune conditions and etc. Might also be worth a look down that road.

I'm pretty extra tired here so hopeful that all made some little bit of sense.

----------

@Path

Mucus - The stuff that comes out our @ss when those of us with IBD poop - could be symptom of bacterial infection, could be a symptom of viral infection, could be a symptom of parasitic infection, could be a symptom of a a change in gene expression... There's lots to support any of those - Or a change in mucus could be the actual problem in the first place.

No one knows really. I have no clue.

Personally I'd like to believe that a bacterial infection causes a change in our mucin production. So in this case it would be a symptom - and I guess at the same time the problem!
Posted 7/3/2014 10:48 AM (GMT 0)

Path:

Without Mark many of my threads would die a short death. He is a tenacious researcher,as you are.

My hope is that with our combined internet brain,we may be able to solve what the research doc's have not

been able to solve in the past 100 years.  After my son's colon was ripped out I lost faith in the Gi communities

ability to fix this disease, medically.

On the subject of soap.

Please explain why it is a problem.

Old Mike

Not related to this post but people should read these papers,posted in the past.

Normal diet not sufficient to restore the mucus in dss colitis,need extra specific amino acids.

http://jn.nutrition.org/content/136/6/1558.full.pdf

This one goes along with the distal start of UC.

http://gut.bmj.com/content/30/12/1660.full.pdf


Post Edited (Old Mike) : 7/3/2014 12:13:38 PM (GMT-6)

Posted 7/3/2014 6:09 PM (GMT 0)
@Maurader - Real quickly:

If CHOP is decreased then PPARy is increased because more C/EBPb binds with PPARy.

PPARy negatively regulates Nf-KB. (Decreases inflammation)

So ER Stress induced CHOP suppresses PPARy transcription by sequestering C/EBPb binding to PPARy promoter.

Due to this - ER stress can enhance NF-kB.

In contrast PPARy counter regulates gut inflammation by attenuating NF-kB activation.

60% decreased expression of PPARγwas observed at the mRNA and protein levels in the colon of UC patients www.hindawi.com/journals/ppar/2012/620839/


I'd like to double check all of the above to make sure it's right. If you spot something wrong let me know. I'm a little interested in this from a bacteria perspective - or ER stress from bacteria
Posted 7/3/2014 6:22 PM (GMT 0)

Canada Mark said...
@marauder

Again, as I mentioned before I think the paper you're referring to showing it down-regulted is specific to bacterial and T-cell mediated colitis...... but actually upregulated in Ulcerative Coltis. So that's causing the first bit of confusion. It's a wording thing. There's a difference between Bacterial Colitis/T-cell mediated colts and actual Ulcerative Colits and that statement is pointing this out and showing down and up regulation respectively.

-------
In regards to the other two papers:

CHOP transcription factors such as C/EBPb & C/EPBa fall downstream under signalling from the IL-17 receptor. IL-17 is a cytokine. When IL-17 binds to it's receptor it sets off a chain of events. This chain of events or molecular signalling ultimately results in NF-kB activation which results in cytokine expression and it also recruits components of the MAP kinase pathway and this results in in enhancing the stability of cytokine mRNA. So again there's a big chain of events... Like anything involving the immune system it's confusing as heck at first and ongoing!

Now - activation of the C/EBP family transcription factors (Transcription factors are proteins and they control DNA to mRNA translation so ultimately they help build specific molecules to respond/induce something) - anyway C/EPB family transcription factors IN ADDITION to up-regulation of NF-kB and members of the MAP kinase pathway, signalling through IL-17RA and IL-17RC proteins has also been shown to activate the transcription factors C/EPBa and C/EPBb, which promote expression of IL-6, one of the quintessential inflammatory cytokines.

So here's the deal: Cytokines (Like IL17 and IL-6 etc) are molecules that communicate among the cells of the immune system. So they basically say or instruct what to do - and ultimately they can instruct a cell when to survive and when to die. We hear a ton about all these in IBD on this site.

Now, getting to the point here - there are loops... much like with toll like receptors. These loops are there to keep check or keep things from spiralling out of control like aberrant cell death or inflammation and such. These loops are controlled by transcription regulation. What the other papers are referring to is the transcription regulators - and this in turn effects CHOP expression and seem to be indicating an increase in this (and other things) in IBD - though they may not mention CHOP directly because they are looking at transcription regulation in bulk.

Also bear in mind IL-6 and IL-17 are often (if not always) detected IBD whereas not in normal controls.

------
At the end of the day - often things go down these crazy immune paths and lead nowhere in relation to IBD except another "way" or route that is a "possible" step that "may" have gone wrong... sorta thing. So I wouldn't spend to much time focusing on it unless it's out of sheer interest or curiosity, which is pretty cool anyway to have a curiosity about things. Who know's what you might stumble upon or think of etc. Perhaps start with noting the genes that regulate transcription factors and work forward from there.

Sorry, source for all of the above - Page 129 Chapter 4 Kirby Immunology Seventh Edition. Might be a good start as well.

I'll take some time not tomorrow but perhaps the ext day or so and maybe search in more detail. I should have some older stuff bookmarked away on here.

Side not - I think (but not sure) that unfolded protein response is implicated in a lot of autoimmune conditions and etc. Might also be worth a look down that road.

I'm pretty extra tired here so hopeful that all made some little bit of sense.

----------

@Path

Mucus - The stuff that comes out our @ss when those of us with IBD poop - could be symptom of bacterial infection, could be a symptom of viral infection, could be a symptom of parasitic infection, could be a symptom of a a change in gene expression... There's lots to support any of those - Or a change in mucus could be the actual problem in the first place.

No one knows really. I have no clue.

Personally I'd like to believe that a bacterial infection causes a change in our mucin production. So in this case it would be a symptom - and I guess at the same time the problem!

1) While I appreciate the literature reviews, if you are doing them just for me you reeally dont have to. I dont want you wasting your time on them. Im a 4th year biochemist and Ive specialized in immunology so I ahve a pretty good foundation on this stuff (in my opinion at least) : p

2) Your right about ER stress being an issue in other autoimmune diseases, but its also an issue in a whole host of others as well, including type 2 diabetes. Its getting a lot of attention lately which is awesome!

3) Ok so I solved the riddle (helps when I actually have time to read the paper). First of all, the title of the original paper holds the answer. " C/EBP homologous protein inhibits tissue repair in response to gut injury and is inversely regulated with chronic inflammation". Inversely regulated means its down-regulated in chronic inflammation. If thats not enough proof, here is an excerpt from the intro of that paper: "Interestingly, studies in UC patients indicate that both CHOP mRNA and protein expression is significantly decreased,28 even though ER UPR and mitochondria UPR were shown to be activated under inflammatory conditions.8, 27" This is EXACTLY what I have been getting at all along. Just because ER stress is activated in UC, it doesnt mean CHOP expression is as well; which it clearly isint. Btw, the data associated with this is shown in the first results section.

Post Edited (Marauder93) : 7/3/2014 12:25:13 PM (GMT-6)

Posted 7/3/2014 10:52 PM (GMT 0)
Do you have a copy of that you can email me? I don't have access to it. All I can read is the abstract! ha

I'd like to double check/clarify the aspect of over expression - and the mouse model they used.

"Chop overexpression increased the susceptibility toward dextran sodium sulfate (DSS)-induced intestinal inflammation and mucosal tissue injury. Furthermore, a delayed recovery from DSS-induced colitis and impaired closure of mechanically induced mucosal wounds was observed."

Also if it's reduced this would have implications on PPARy

EDIT: Also this statement in the opener for the abstract "Loss of intestinal epithelial cell (IEC) homeostasis and apoptosis negatively affect intestinal barrier function." But from a bacterial perspective.

EDIT EDIT: Also if it's reduced then this goes against the delayed healing aspect of the paper. Normally higher levels of CHOP would activate apoptosis - as in the above stuff in regards to stress response. It seems to me these guys are suggesting/demonstrating that higher levels of CHOP in Chronic inflammation bypass apoptosis and delay healing i.e Impaired closure of mechanically induces mucosal wounds.

Post Edited (Canada Mark) : 7/3/2014 5:32:15 PM (GMT-6)

Posted 7/4/2014 12:52 AM (GMT 0)
I agree we should all try working together. UC is a disease with a lot of unkowns. If someone thinks they know it all and have all the answers then they should apply for a patent or the Nobel prize and we can shut this website down. Until then I appreciate all the hard work that CM, Old Mike, and others are doing. I get in those research moods from time to time until my brain suffers an information overload and then I quit for a few months to recuperate. This disease can give you a real headache.
Posted 7/4/2014 2:14 PM (GMT 0)
Ditto what Gary said!
But if someone is wrong they should acknowledge it and move on so that we don't get stuck on things and not get anywhere.
Posted 7/4/2014 3:38 PM (GMT 0)
alright, you got me.. Im grumpy and should have never popped into this thread. because of the way CM treated me I have very little objective lens for him which is why I should keep my ignore list active. I just have no patience. But that is my personal problem at this point hopefully and CM will stop with how he has treated me in the past and never do it to anyone else. I feel the need to warn others because I truly feel it was so egregious to say the things he has to me and attack me the way he did. Yes, I did get quite snippy after. But truly the attacks were unstable and just plain ugly and they revealed a dangerous level of either spite, pride or scientific confusion. I hate leaving this place in those hands. Hate hate hate.

But that is a personal problem and I am unable to save the world. So Ive said my piece on it and I wont say it again. Its a shame in a few days that that warning really means nothing in digital forum land. Im sorry for letting my personal frustation spill into this thread.


And every time I get sucked into the internet my patience gets less and less. But my heart for all of you stuck here hurts more and more.. But I cant save the world, right?

Have fun with your debates.
Posted 7/4/2014 4:52 PM (GMT 0)
I don't want this to sound the wrong way because you have a lot of knowledge and are right about many things, but, sometimes you come off as being arrogant in thinking that your knowledge is so great that you can actually save the world if everyone would just listen and take your advice. There are a lot of people that know a lot about UC, including many medical professionals, but I have yet to see anyone who has the answer to UC.
Posted 7/4/2014 5:28 PM (GMT 0)

Canada Mark said...
Do you have a copy of that you can email me? I don't have access to it. All I can read is the abstract! ha

I'd like to double check/clarify the aspect of over expression - and the mouse model they used.

"Chop overexpression increased the susceptibility toward dextran sodium sulfate (DSS)-induced intestinal inflammation and mucosal tissue injury. Furthermore, a delayed recovery from DSS-induced colitis and impaired closure of mechanically induced mucosal wounds was observed."

Also if it's reduced this would have implications on PPARy

EDIT: Also this statement in the opener for the abstract "Loss of intestinal epithelial cell (IEC) homeostasis and apoptosis negatively affect intestinal barrier function." But from a bacterial perspective.

EDIT EDIT: Also if it's reduced then this goes against the delayed healing aspect of the paper. Normally higher levels of CHOP would activate apoptosis - as in the above stuff in regards to stress response. It seems to me these guys are suggesting/demonstrating that higher levels of CHOP in Chronic inflammation bypass apoptosis and delay healing i.e Impaired closure of mechanically induces mucosal wounds.

1) Absolutely, Ill send the PDF. Is there any way to add it to the post, because I dont see an email listed for you CM?

2) The first quoted part is still true; when CHOP is over-expressed, those observations hold. Its just that in UC its not over-expressed. This is actually the same thing we see with 5-HT.

3) With regard to your last point, Im not really sure if there observations are relevant to UC at all tbh. I mean, maybe they can manipulate the pathway, but as it stands CHOP is already down-regulated and thus (presumably) not causing an issue in us
Posted 7/4/2014 5:28 PM (GMT 0)
I am grateful to all of you who research this issue. No one is more motivated to find a cure than the gang on here who suffer with this crap. This stuff is out of my league but I am happy that our healingwell researchers are working on it. Keep it up guys!
Posted 7/4/2014 7:27 PM (GMT 0)
@Maurader

Been thinking about this all day at work cause it doesn’t add up.

I still don’t agree with your take on it and I think perhaps you misread/misunderstood something (no offence) but let me justify why first - www.ncbi.nlm.nih.gov/pubmed/21864296 This shows exactly that. Elevated CHOP and associated proteins/genes in active UC. There’s more studies as well including the one posted earlier. This is also the case in many other diseases and studies revolving around them.

So it would surprise the heck out of me and many others of course; and perhaps, especially the researchers who conducted these studies if this was NOT in fact the case and CHOP was/is actually down-regulated in mucosal samples of active IBD.

Even in almost remission or inactive it’s still slightly elevated in all the studies.

Based on the above - I’d bet my last dollar that they are actually referring to samples in remission or adjacent to UC inflammation sites or something. Can you look and verify perhaps? Please.

The title would make a lot more sense as well! Inverse means opposite - so NOT opposite meaning “down-regulated" in IBD - but opposite in intended and perceived “function”. and then both the study and the article would make a heck of a lot more sense and be in-line with current observations. Otherwise, it just does not.

Maybe take a second and see if they tested active or remission/healthy/adjacent to inflammation UC samples. This will ultimately give us the answer and clarify the issue. Again, if they didn't sample active or diseased then everything makes a ton of sense.

Post Edited (Canada Mark) : 7/4/2014 6:00:40 PM (GMT-6)

Posted 7/4/2014 8:41 PM (GMT 0)
Thanks, it's cool - I asked Professor Tan to send it, so I'll get it on Sunday when he get's back. It's of interest to him anyway (air quality and health effects).

PS: In thinking about it just now - In contrast to your suggestion of "down-regulation" versus what I am suggesting is really "opposite function" (so anti-apoptosis vs. pro-apoptosis) in chronic inflammation makes far more sense in Colonic Cancer susceptibility in UC based on the reasoning I gave above. Otherwise it does not. Cancer cells just don't want to die like normal cells... This would perhaps explain in part why there is perhaps an increase in cancer risk to those with even microscopic chronic inflammation.

Note: 5HT is most definitely altered in some IBD - you have to look to SERT. We all spent ages on this on here a short while ago so there's tons filed away on here in this regard. There's a few biopsy papers posted on here that show increased levels in IBD biopsy samples. Also 5HT is regulated by SERT so that comes into play.
Posted 7/4/2014 8:48 PM (GMT 0)

Canada Mark said...
@Maurader

Been thinking about this all day at work cause it doesn’t add up.

I still don’t agree with your take on it and I think perhaps you misread/misunderstood something (no offence) but let me justify why first:

There’s many studies showing CHOP and associated proteins elevated in active inflammation in IBD, especially UC. Here is a good example repub.eur.nl/pub/38603/130130_Deuring,%20J.%20Jasper.pdf Page 104. This shows exactly that. Elevated CHOP and associated proteins/genes in active UC. There’s more studies as well including the one posted earlier. This is also the case in many other diseases and studies revolving around them.

So it would surprise the heck out of me and many others of course; and perhaps, especially the researchers who conducted these studies if this was NOT in fact the case and CHOP was/is actually down-regulated in mucosal samples of active IBD.

Even in almost remission or inactive it’s still slightly elevated in all the studies.

Based on the above - I’d bet my last dollar that they are actually referring to samples in remission or adjacent to UC inflammation sites or something. Can you look and verify perhaps? Please.

The title would make a lot more sense as well! Inverse means opposite - so NOT opposite meaning “down-regulated" in IBD - but opposite in intended and perceived “function”. and then both the study and the article would make a heck of a lot more sense and be in-line with current observations. Otherwise, it just does not.

Maybe take a second and see if they tested active or remission/healthy/adjacent to inflammation UC samples. This will ultimately give us the answer and clarify the issue. Again, if they didn't sample active or diseased then everything makes a ton of sense.

1) Sorry your link didnt work. Can you post the name of the paper? Ill look it over myself.

2) Do these "other studies" you are referring to look at CHOP expression in human UC samples or just animal models? Because as you know, there are huge differences. Again, 5-HT is a PERFECT example of this sort of anomaly. Animal models show a positive correlation between colitis and 5-HT, while human studies (or at least one that I remember off hand) show a negative correlation.

3) There may be other studies out there showing competing results, but my interpretation of this paper (and its cited papers) is spot on. Let me show you some quotes right from the paper that should make it clear:

3a) Interestingly, studies in UC patients indicate that both CHOP mRNA and protein expression is significantly decreased,28 even though ER UPR and mitochondria UPR were shown to be activated under inflammatory conditions.8, 27

3b) Previous studies with UC patients have shown that both CHOP mRNA and protein expression is downregulated in colonic tissue under inflammatory conditions.28

So these studies look at inflamed UC patient biopsy samples. They almost never look at non-inflamed UC tissue unless it is as a control, but that is irrelevant in this case.

4) Dont get too caught up on the title; it again is very clear. When it says CHOP expression is inversely regulated with chronic inflammation it means that as one increases (inflammation) the other decreases (CHOP expression). There is no other way to interpret that. Plus, this is EXACTLY what their most prominent data shows.

Now, Im not saying that what this paper shows is true; you know as well as I that not everything that gets published can be taken as fact. There is too much crapty research methodology or constraints to have much faith at all. So if you have other papers that show increased CHOP expression in human colonic tissue samples from UC patients, then we have to evaluate the studies' methodologies and decide which is more valid.
Posted 7/4/2014 10:55 PM (GMT 0)
I fixed the way to access the link. All studies on CHOP show it elevated in active IBD to date. All are in human samples. Here is one of them in human www.ncbi.nlm.nih.gov/pubmed/21864296 as are all the others.

5HT is NOT the perfect example. There are many human studies in IBD. I sent you one link already on another thread a while ago. There's many more.

5 minutes on google and you'll find this on both CHOP and 5HT.

And no, it doesn't mean that either. It means that they are clarifying the Regulation of CHOP protein expression in injury and stress and that in, or from, a viewpoint of chronic inflammation the regulation is inverse to what would be normally expected. The result of this inverse relationship is actually delayed healing.

EDIT: Sorry I typed that super quick cause I was getting work phone calls so it maybe sounded harsh. What I mean is that in the context of all the other studies on chop and associated proteins, that this is an unexpected result - but there is another study on heart disease I think it was that sort of implies this very thing but they didn't make the connection. What they found in a way was somewhat opposite where an increase in chop just after injury helped heal versus delay. I'm kicking myself now for not bookmarking it but will find it. Or I'm 90% sure this is what it said.

It's all interesting stuff really. What I did learn last night however it that expression is regulated differently within a multitude of different cell types.

I wish I could find out if the samples from the citation were from active IBD or I guess UC. My gut says they are not from active UC sites because of all of the above.

In regards to 5HT there are a few - and they are human and animal. It's easy to find them via a quick google search. Some you will notice that an increase is 5HT is not present in all with IBD. But in IBS it's pretty standard - so this has some interesting implications.

Post Edited (Canada Mark) : 7/4/2014 6:51:36 PM (GMT-6)

Posted 7/5/2014 5:04 AM (GMT 0)

Canada Mark said...
I fixed the way to access the link. All studies on CHOP show it elevated in active IBD to date. All are in human samples. Here is one of them in human www.ncbi.nlm.nih.gov/pubmed/21864296 as are all the others.

5HT is NOT the perfect example. There are many human studies in IBD. I sent you one link already on another thread a while ago. There's many more.

5 minutes on google and you'll find this on both CHOP and 5HT.

And no, it doesn't mean that either. It means that they are clarifying the Regulation of CHOP protein expression in injury and stress and that in, or from, a viewpoint of chronic inflammation the regulation is inverse to what would be normally expected. The result of this inverse relationship is actually delayed healing.

EDIT: Sorry I typed that super quick cause I was getting work phone calls so it maybe sounded harsh. What I mean is that in the context of all the other studies on chop and associated proteins, that this is an unexpected result - but there is another study on heart disease I think it was that sort of implies this very thing but they didn't make the connection. What they found in a way was somewhat opposite where an increase in chop just after injury helped heal versus delay. I'm kicking myself now for not bookmarking it but will find it. Or I'm 90% sure this is what it said.

It's all interesting stuff really. What I did learn last night however it that expression is regulated differently within a multitude of different cell types.

I wish I could find out if the samples from the citation were from active IBD or I guess UC. My gut says they are not from active UC sites because of all of the above.

In regards to 5HT there are a few - and they are human and animal. It's easy to find them via a quick google search. Some you will notice that an increase is 5HT is not present in all with IBD. But in IBS it's pretty standard - so this has some interesting implications.

1) Ill have a look at the links in the morning; but if they do show an increase in CHOP expression in active IBD then we have to do what I said before and evaluate the validity of the studies. You cant just go by # vs #.

2) 5-HT is a perfect analogy for this because in animal models of colitis it is always up-regulated, while in humans, it is sometimes up and sometimes down; exactly like CHOP is. Trust me, my lab is one of the world experts on the role of 5-HT in the colon and I have read pretty much every paper on the subject.

3) I can tell you with 100% certainty that the "inverse" isint with respect to what they THOUGHT....no one would EVER write that in a paper....it wouldnt make any sense at all first of all. And secondly, the data AND the discussion clearly show that the relationship is as I said before (at least according to this paper)... Its a VERY VERY black and white interpretation, you shouldnt be over thinking it this much.

4) The samples were definitely from active UC... Firstly, it wouldnt make sense to use non-inflamed tissue when you are studying UC and secondly, it would be an out right lie and fabrication to claim a specific fact about UC without using UC tissue...it would just never happen

5) In response to your other post that I missed; the role of SERT in IBD is relatively minimal. It could potentially serve as a therapeutic target, but the main area of interest is 5-HT signalling via the 7 5-HT receptors. I actually just donated a biopsy sample for a study looking at this very thing

Post Edited (Marauder93) : 7/4/2014 11:07:03 PM (GMT-6)

Posted 7/5/2014 5:58 AM (GMT 0)
It's cool, I'll have it Sunday at some point anyway. I was just curios on the samples most likely being not from active UC. It's pretty simple to figure out without looking/reading to be honest after thinking about it today.

I'm quite sure the title means what I said, it's not what they "thought" it's what actually occurs; Inverse Regulation.

I was only interested in this from a totally different perspective anyway - DDS and possible bacterial implications in regards to another topic altogether and implications on increased cancer risk in UC.

PS - it's the long weekend for you guys I think! Or Fourth of July weekend so don't spend it reading and go enjoy the festivities and sunshine and such... Hopefully you're not to ill for that.

And good luck with the WOO thing! Hopefully it helps but I really don't know anyone with straight UC that it has... Which sucks. It's mostly pancolitis. Frustrating.

Post Edited (Canada Mark) : 7/5/2014 12:52:41 AM (GMT-6)

Posted 7/5/2014 7:39 AM (GMT 0)
Hi There,

I was reading this forum a lot during the last years. I am from Germany with light/moderate UC. I read about the PC discussion and have promising news for you. We discuss this approach in Germany a lot and have several success stories. A few pharmacies are already selling Phosphatidylcholine as it is a "normal" supplement in Germany.

01 Phosphatidylcholine

Prof. Stremmel currently initiated a final phase III study to compare patients with active UC and disease modifying treatment of mesalazin added with pc vs. placebo. We have a lot of stories of severe cases with healed colons. However, this is also very intensively discussed - it is not working for all patients. Some have an intermediate form of UC/MC or the barriere is not the cause. It takes about 3-5 months to work and some need rather high doses of PC (3g is recommended, I know cases with 20g a day - who are symptom free now).

From my perspective, I work at healthcare and reviewed all available studies as well as resources, PC will become one major treatment for basic UC patients within the next years.

02 Parameters to check your disease

I recently visited Dr. Swidsinski from Charité which is a very famous Clinic University in Germany and discussed his publications. His parameter based approach is very promising and gets impressive results:

You already shared this link: http://www.charite.de/arbmkl/themen/ubersicht/polensascha.pdf

Several KOLs referred to the full publication. If you visit his website - sorry - it is in German, he explains how to track your inflammation by bacteria layers on your stool. I discussed this issue with a lot of patients and all of them were able to get the disease under control.

http://www.charite.de/arbmkl/patienten/patientenaufklarung.pdf (scroll down, page 5).

All the best,
GermanOne

Post Edited (GermanOne) : 7/5/2014 1:47:14 AM (GMT-6)

Posted 7/5/2014 9:30 AM (GMT 0)
GermanOne, thank you.
http://www.ncbi.nlm.nih.gov/pubmed/24796768
Posted 7/5/2014 2:19 PM (GMT 0)
This is all interesting. Is it my imagination that colonoscopies never really mention anything about the mucusal layer itself? If so, I wonder why not? Do the preps have any effect on the mucusal layer? I mean, when we do a prep does that destroy valuable evidence?
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