IFN-gamma induces transglutaminase 2 expression in rat small intestinal cells.
Transglutaminase 2 (tissue transglutaminase, TGase 2) was recently identified as an endomysial autoantigen in celiac disease (CD). Identification of how TGase 2 expression is increased may allow a better understanding of this autoimmune disease. Certain inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), and the Th type I cytokine interferon-gamma (INF-gamma) are abundant in CD. We have investigated whether these play a role in the regulation of TGase 2 expression in a model rat small intestinal epithelial cell line (IEC-6). After treatment for 24 h, TNF-alpha did not significantly alter TGase 2 mRNA or activity, but TGF-beta decreased mRNA and activity by 4-5-fold. IFN-gamma increased mRNA and TGase 2 activity by about 2-fold in 24 h and 5-fold by 5 days. Our new data suggest that increased TGase 2 expression in the upper small intestine of CD patients may be due to increased IFN-gamma expression, loss of TGF-beta signaling, or both.
Kim
Soo-Youl
SY
Weill Medical College of Cornell University, Burke Medical Research Institute, White Plains, NY 10605, USA. sykim@burke.org
Jeong
Eun-Joo
EJ
Steinert
Peter M
PM
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007421:Intestine, Small / Q000201:enzymology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D012333:RNA, Messenger; D011994:Recombinant Proteins; C000717609:Tgm2 protein, rat; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins