Transglutaminase 2 in inflammation.
Many reports have shown that the expression of transglutaminase 2 (TG 2) is increased in inflammatory diseases. Although during the last several decades multiple physiological roles for TG 2 have been demonstrated in various cell types, its role in the inflammatory process is not yet clear. TG 2 is a crosslinking enzyme that is widely used in many biological systems for tissue stabilization purposes and immediate defense against injury or infection. Aberrant activation of TG 2 activity in tissues contributes to a variety of diseases including neurodegenerative diseases, autoimmune diseases, and cancers. In most cases, TG 2 appears to form an inappropriate protein aggregate that may be cytotoxic enough to trigger inflammation and/or apoptosis. In some cases, such as celiac disease and rheumatoid arthritis, TG 2 is also associated with the pathogenic progression, as well as in the generation of autoantibodies. Recently, we discovered that increased TG 2 activity triggers NF-kappaB activation without I-kappaBalpha kinase signaling. TG 2 induces the polymerization of I-kappaBalpha rather than stimulating I-kappaBalpha kinase. This polymerization of I-kappaB results in the direct activation of NF-kappaB in various cell lines. We also found that TG inhibition reverses NF-kappaB activation. Interestingly, this coincides with the reversal of inflammation in conjunctivitis models by treatment with TG 2 inhibitors. Here, I introduce a new role for TG 2 as a signal modulator, which may suggest a new paradigm for the inflammatory process.
Kim
Soo-Youl
SY
Division of Basic Science, Research Institute, National Cancer Center, Goyang, Republic of Korea. kimsooyoul@gmail.com
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000201:enzymology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D006737:Horseshoe Crabs / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D008264:Macrophages / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins