Anti-inflammatory Benzene Diamine Compound Inhibited Toll-Like Receptor 4-Mediated Inducible Nitric Oxide Synthase Expression and Nuclear Factor-KappaB Activation

Abstract

Toll-like receptor 4 (TLR4) is known to play an important role in innate immune responses. In the present study, chemically synthetic compound of N¹-benzyl-4-methylbenzene-1,2-diamine (BMD) was discovered to inhibit nitric oxide (NO) production in macrophages RAW 264.7 stimulated with lipopolysaccharide (LPS) or fibronectin as TLR4 activators. The BMD compound attenuated LPS-induced synthesis of both mRNA and protein of NO synthase (iNOS), and inhibited LPS or fibronectin-mediated iNOS promoter activity, indicating that the compound down-regulated iNOS expression at transcription level. As a mode of the anti-inflammatory action shown by BMD compound, inhibitory effect on nuclear factor (NF)-κB activation was also investigated in macrophages RAW 264.7 stimulated with the TLR4 activators.