Biochemical and Biophysical Research Communications, Vol.323, No.3, 1055-1062, 2004
Transglutaminase 2 induces nitric oxide synthesis in BV-2 microglia
A hallmark of brain inflammation is the activation of microglia. Excessive production of nitric oxide (NO), as a consequence of increased inducible nitric oxide synthase (iNOS) in glia, contributes to neurodegeneration. Transglutaminase 2 (TGase 2) is a crosslinking enzyme, which is increased in neurodegeneration. TGase 2 is also considered to be a useful and reliable marker for activation levels in resident and inflammatory macrophages. Therefore, an increase of TGase 2 expression may contribute to activation of microglia. To test this hypothesis, we analyzed the expression of TGase 2 in BV-2 microglia activated with lipopolysaccharide (LPS). Total TGase activity was increased about 5-fold after 24 h exposure to LPS. The increase of NO synthesis is correlated with increase of TGase 2 expression. Secretion of NO was reduced between 40 and 80% by TGase inhibition in a dose-dependent mariner. This suggests that TGase 2 appears to control iNOS transcription. (C) 2004 Elsevier Inc. All rights reserved.