Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis |
| |
Authors: | K.?Schlottmann,F.-P.?Wachs,J.?Grossmann,D.?Vogl,M.?Maendel,W.?Falk,J.?Sch?lmerich,T.?Andus,G.?Rogler author-information" > author-information__contact u-icon-before" > mailto:gerhard.rogler@klinik.uni-regensburg.de" title=" gerhard.rogler@klinik.uni-regensburg.de" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
| |
Affiliation: | (1) Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany |
| |
Abstract: | BACKGROUND: In acute or chronic inflammatory bowel disease (IBD) interferon gamma (IFNgamma) is still considered to be an important pro-inflammatory mediator. In the present study we investigated the impact of IFNgamma on interleukin-8 (IL-8) production as a read-out for cell activation in intestinal epithelial cell (IEC) lines and primary human colonic epithelial cells (CEC). METHODS: Primary cultures of human CEC were established from the mucosa of patients without inflammatory disease. CEC, HT-29 or Caco-2 cells were incubated with either IFNgamma, tumor necrosis factor (TNF)alpha or IL-10. IL-8 and IL-1Ra secretion was determined by ELISA. Competicon PCR was used for quantification of IL-8mRNA. Apoptosis was quantified by propidium iodine incorporation and fluorescence activated cell sorting (FACS) analysis. RESULTS: In contrast to HT-29 cells in primary human CEC 100 U/ml IFNgamma inhibited IL-8 secretion significantly to 70+/-15% of unstimulated primary CEC (p<0.005) more effectively than IL-10 (87+/-21% versus unstimulated cells, n.s.). In HT-29 cells, IL-8 secretion was induced to 405+/-101% of unstimulated cells. In Caco-2 cells, IFNgamma had no significant effect on IL-8 secretion. The effect in HT-29 and CEC was concentration dependent. In primary CEC, 200 U/ml IFNgamma further reduced IL-8 secretion to 48+/-18% of unstimulated CEC (p<0.05). Whereas IL-8 mRNA was strongly upregulated in HT-29 cells, no upregulation or even a downregulation was found in CEC. Pre-incubation with 100 U/ml IFNgamma did not increase the susceptibility to apoptosis mediated by anti-Fas antibody (CH-11) in primary CEC, whereas HT-29 cells showed increased rates of apoptosis after priming with IFNgamma. CONCLUSION: In contrast to HT-29, IFNgamma downregulated IL-8 secretion and did not induce IL-8 mRNA expression in primary human CEC. This effect was not due to induction of apoptosis. |
| |
Keywords: | Apoptosis IFN /content/rvj8dbrxdubl8d2a/xxlarge947.gif" alt=" gamma" align=" MIDDLE" BORDER=" 0" > IL-8 Inflammation Intestinal epithelial cells |
本文献已被 PubMed SpringerLink 等数据库收录! |
|