Abstract
The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.
Highlights
Inflammation is a major component of the innate immune response to harmful stimuli, such as pathogen infection, and is related to many pathophysiological processes [1,2]
We investigated whether pseudane-VII could regulate the expression of pro-inflammatory cytokines including IL-1β, tumor necrosis factor (TNF)-α and IL-6 in LPS-activated macrophages
mitogen-activated protein kinase (MAPK) such as ERK1/2, p38 and JNK are generally activated by TLR4 receptor and sequentially trigger nuclear factor (NF)-κB phosphorylation and translocation in some mammalian cells [15,16]
Summary
Inflammation is a major component of the innate immune response to harmful stimuli, such as pathogen infection, and is related to many pathophysiological processes [1,2]. Macrophages stimulated by inflammatory stimuli produce pro-inflammatory factors, such as cytokines and nitric oxide (NO) [3]. Mar. Drugs 2017, 15, 336 under various inflammatory conditions that is up-regulated by inflammatory stimuli including lipopolysaccharide (LPS), and it can lead to excessive NO production by activated macrophages [7,8]. Pseudane-VII is a novel compound that is a secondary metabolite of Pseudoalteromonas sp. This study was performed to elucidate the anti-inflammatory effects of pseudane-VII on LPS-stimulated macrophages and to examine the potential mechanisms by which pseudane-VII regulates NO production. We investigated whether pseudane-VII could regulate the expression of pro-inflammatory cytokines including IL-1β, TNF-α and IL-6 in LPS-activated macrophages. Pseudane-VII reduced LPS-induced NO production and pro-inflammatory cytokine expression in macrophages by decreasing ERK, JNK, and p38 MAPK phosphorylation
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