αAL14, a novel peptide, has anti-inflammatory effects on LPS-stimulated RAW264.7 cells through inhibiting ERK/MAPK and NF-κB pathway.

Abstract

A novel model peptide, αAL14, has showed several bioactivities such as anti-angiogenic and anti-cancer activity in previous researches. In this study, we investigated anti-inflammatory properties of αAL14 in LPS-stimulated RAW264.7 macrophages. Although αAL14 had no significant effect on cell viability in RAW264.7 cells it decreased production of pro-inflammatory mediators, NO and PGE2 production in LPS-stimulated RAW264.7 cells. Moreover, αAL14 regulated expression of iNOS and COX-2 and decreased transcriptional level of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6 compared to LPS only-treated cells. In MAPKs, only phosphorylation of ERK1/2 was suppressed in presence of αAL14, but not those of p38 and JNK/SAPK in LPS-stimulated RAW264.7 cells. Moreover, phosphorylation of NF-κB was inhibited and translocation of both p-ERK1/2 and NF-κB to nucleus was inhibited by αAL14 treatment. Phosphorylation and degradation of IκBα was suppressed in αAL14-treated RAW264.7 cells. Therefore, attenuated phosphorylation of ERK and NF-κB by αAL14 treatment can result in decreased expression of pro-inflammatory mediators such as NO, PGE2 and pro-inflammatory cytokines in LPS-stimulated RAW264.7 cells. Consequently, we suggest that αAL14 possesses abilities to inhibit inflammatory responses in LPS-stimulated RAW264.7 macrophages.