Anti-inflammatory benzene diamine compound inhibited toll-like receptor 4-mediated inducible nitric oxide synthase expression and nuclear factor-kappa B activation.
Toll-like receptor 4 (TLR4) is known to play an important role in innate immune responses. In the present study, chemically synthetic compound of N(1)-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)-kappaB activation was also investigated in macrophages RAW 264.7 stimulated with the TLR4 activators.
Kim
Byung Hak
BH
College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea.
Shin
Hyun-Mo
HM
Jung
Sang-Hun
SH
Yoon
Young-Gahp
YG
Min
Kyung Rak
KR
Kim
Youngsoo
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003959:Diamines; D004791:Enzyme Inhibitors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D001554:Benzene