Does cytosolic phospholipase A2 regulate TNF-induced production of joint destructive effectors in synoviocytes?
cPLA2α appears to be an important regulator of central effectors of inflammation and joint destruction, namely MMP3, IL8, COX2, and PGE2. Decreased transcription of the PLA2G4A and COX2 genes in response to cPLA2α enzyme inhibition further suggest a self-reinforcing effect of cPLA2α inhibition in response to TNF. Collectively, these results support that cPLA2α is an attractive therapeutic target candidate as its inhibition reduces the production of multiple key pro-inflammatory factors involved in RA pathogenesis.
Bile-pancreatic juice exclusion from gut increases p38(MAPK) activation and TNF-alpha production in this experimental model. Our findings support our central hypothesis that bile-pancreatic juice exclusion exacerbates cell stress and acute inflammation in ligation-induced acute pancreatitis.