New target against inflammatory diseases: transglutaminase 2

Transglutaminase (TGase) 2 is an enzyme that is widely used in many biological systems for generic tissue stabilization or immediate defense for wounds. Many reports showed that TGase 2 is aberrantly activated in tissues and cells and contributes to a variety of diseases, including neurodegenerative diseases and autoimmune diseases. In most cases, TGase 2 appears to be a factor in the formation of inappropriate proteinaceous aggregates that may be cytotoxic. However, in other cases, such as celiac disease, arthritis, lupus, and amyotrophic lateral sclerosis, TGase 2 is involved in the generation of autoantibodies. This suggests the possibility that inappropriate expression and/or presentation of TGase 2 to T cells might contribute to these diseases in genetically predisposed individuals. We and others have found that TGase 2 expression is also increased in the inflammation process. Furthermore, we also demonstrated a reversal of inflammation by TGase inhibition. This review will examine a possibility of TGase inhibitors as therapeutic agents in a variety of inflammatory diseases.