# IFN-{gamma} and TNF-{alpha} decrease serotonin transporter function and expression in



## eric (Jul 8, 1999)

Am J Physiol Gastrointest Liver Physiol. 2006 Dec 14; [Epub ahead of print] Links IFN-{gamma} and TNF-{alpha} decrease serotonin transporter function and expression in intestinal epithelial cells.Foley KF, Pantano C, Ciolino A, Mawe GM. Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, Vermont, United States.Recent studies have shown that mucosal serotonin transporter (SERT) expression is decreased in animal models of colitis, as well as in the colonic mucosa of humans with ulcerative colitis (UC) and irritable bowel syndrome (IBS). Altered serotonin transporter function or expression may underlie the altered motility, secretion, and sensation seen in these inflammatory gut disorders. In an effort to elucidate possible mediators of SERT down-regulation, we treated cultured colonic epithelial cells (Caco2) with conditioned media from activated human lymphocytes. Application of the conditioned media caused a decrease in fluoxetine-sensitive [(3)H]5-HT uptake. Individual pro-inflammatory agents were then tested for their ability to affect uptake. Cells were treated for 48 to 72 hours with PGE2 (10uM), IFN-gamma (500 ng/ml), TNF-alpha (50 ng/ml), IL-12 (50 ng/ml) or the nitric oxide releasing agent GSNO (100 microM). [(3)H]5-HT uptake was then measured. Neither PGE nor IL-12 had any effect on [(3)H]5-HT uptake, and GSNO increased uptake. However, after 3 days incubation, both TNF-alpha and IFN-gamma elicited significant decreases in SERT function. Neither TNF-alpha nor IFN-gamma were cytotoxic when used for this period of time and at these concentrations. These two cytokines also induced decreases in SERT mRNA and protein levels. By altering SERT expression, TNF-alpha and IFN-gamma could contribute to the altered motility and expression seen in vivo in UC or IBS. Key words: SERT, serotonin, colitis, IBD, enteric nervous system.PMID: 17170025


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## Nanobug (Nov 7, 2006)

> quote:IFN-{gamma} and TNF-{alpha} decrease serotonin transporter function and expression in intestinal epithelial cells


Assuming I'm reading this correctly, this article is very interesting in that it shows that inflammation could be the cause of altered gut motility. Instead of the fuzzy "functional" label, we would have something more tangible and measurable, maybe testing for elevated levels of C-reactive protein (my case) and/or fibrinogen. And, if this inflammation in some cases is caused by nasty bugs in one's bowels, it could explain why antibiotics "cured" my IBS-D and skin rashes: no more inflammatory cytokines causing havoc in my system.


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