마우스 세포에서 D-(+)-Cycloserine의 항염증 및 멜라닌생성 억제효과 규명

Abstract

Recently, additional therapeutic potentials of classical antibiotics are gaining considerable attention. The discovery of penicillin in the 1920s had a major i mpact on the history of human health. Penicillin has been used for the treatm ent for fatal microbial infections in humans and has led to the discovery of s everal new antibiotics. D-(+)-cycloserine (DCS) is an antibiotic isolated from Streptomyces orchidaceous and is used in conjunction with other drugs in the treatment of tuberculosis. To determine whether DCS has anti-inflammatory a nd anti-melanogenic effects, we investigated the ability of DCS in lipopolysac charide (LPS)-induced RAW 264.7 macrophages and α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells. DCS inhibited the product ion of nitric oxide (NO), prostaglandin E2 (PGE2) and the expression of proinf lammatory cytokines such as interleukin-1β (IL-1β), and interleukin-6 (IL-6) in a concentration-dependent manner. However, it had no effect on the expres sion of TNF-α. Consistent with these findings, Western blot analysis demonst rated that DCS inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase type-2 (COX-2) expression via inhibition of phosphorylati on of inhibitory kappa B-α (IκB-α) through down-regulation of phosphorylate d Akt, ERK and p38. Furthermore, DCS markedly inhibited melanin synthesis and tyrosinase activity in concentration-dependent manner. Western blotting s howed that DCS treatment inhibited the expression of tyrosinase (TYR), tyros inase-related protein 1 (TRP-1) and tyrosine-related protein 2 (TRP-2) via in hibition of microphthalmia-associated transcription factor (MITF) expression. These results indicate that DCS may be used as potential drugs for the treat ment of inflammatory diseases and as melanogenesis inhibitor.