Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating the arachidonic acid pathway in murine macrophages.

ABSTRACT: The bacterial endotoxin lipopolysaccharide (LPS) is known to induce release of arachidonic acid (AA) and its metabolic products, which play important roles in the inflammatory process. We have shown earlier that LPS-induced signals in macrophages are mediated by aldose reductase (AR). Here we have investigated the role of AR in LPS-induced release of AA metabolites and their modulation using a potent pharmacological inhibitor, fidarestat, and AR siRNA ablation in RAW264.7 macrophages and AR-knockout mouse peritoneal macrophages and heart tissue. Inhibition or genetic ablation of AR prevented the LPS-induced synthesis and release of AA metabolites such as PGE2, TXB, PGI2, and LTBs in macrophages. LPS-induced activation of cPLA2 was also prevented by AR inhibition. Similarly, AR inhibition a

SUBMITTER: Shoeb M 

PROVIDER: S-EPMC3188329 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature