(E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine inhibits Inducible Nitric Oxide Synthase Expression in RAW264.7 Macrophages Stimulated with Lipopolysaccharide

Abstract

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. TLR4 has been identified as the receptor for lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. The activation of TLR4 signaling by LPS leads to the activation of NF-κB and the expression of pro-inflammatory gene products such as cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). To evaluate the therapeutic potential of (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), previously synthesized in our laboratory,NF-κB activation and iNOS and COX-2 expression induced by LPS were examined. NVPP inhibited the activation of NF-κB induced by LPS. NVPP also suppressed the iNOS expression induced by LPS but it did not suppress COX-2expression induced by LPS. These results suggest that NVPP has the specific mechanism for anti-inflammatory responses.