Anti-inflammatory effect of Streptochlorin via TRIF-dependent signaling pathways in cellular and mouse models.

Do-Wan Shim,Tae-Bong Kang,Eun-Jeong Shim,Xiao Sun,Tack-Joong Kim,Woo-Young Shin,Hee Shin,Ji-Won Han,Kwang-Ho Lee

doi:10.3390/ijms16046902

Abstract

Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Streptochlorin attenuated the production of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1β, and IL-6 in LPS-stimulated RAW264.7 cells through inhibition of the Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling pathway. Furthermore, streptochlorin suppressed the infiltration of immune cells such as neutrophils into the lung and proinflammatory cytokine production such as IL-6 and TNF-α in broncho-alveolar lavage fluid (BALF) in the LPS-induced acute lung injury (ALI) mouse model. Streptochlorin has potent anti-inflammatory effects through regulating TRIF-dependent signaling pathways, suggesting that streptochlorin may provide a valuable therapeutic strategy in treating various inflammatory diseases.

Highlights

Inflammation is a host defense mechanism against pathogens, but chronic inflammation is related to many diseases such as inflammatory bowel disease and rheumatoid arthritis [1]
Streptochlorin at concentrations up to 100 μM did not affect the viability of RAW264.7 cells
The maximum concentration of streptochlorin was used at 50 μM for the following analyses

Summary

Introduction

Inflammation is a host defense mechanism against pathogens, but chronic inflammation is related to many diseases such as inflammatory bowel disease and rheumatoid arthritis [1]. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4) and leads to the activation of two different signal pathways, MyD88- and Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways [3]. The TRIF-dependent signaling pathway induces the activation of the interferon regulatory factor (IRF3), the transcriptional regulator, the late-phase activation of NF-κB, and mitogen-activated protein kinase (MAPK) [4,5]. The TRIF-dependent signaling pathway induces inflammatory cytokines and Type I interferons (IFNs) and IFN-inducible genes [6,7]. We have previously reported that streptochlorin has anti-allergic activity in RBL-2H3 cells [12]. We report the anti-inflammatory effects of streptochlorin and underlying mechanisms involved in both cellular and animal models

Results and Discussion

Streptochlorin Ameliorated LPS-Induced ALI in Mice

Reagents and Antibodies

Cell Culture

Animals and LPS-Induced ALI Mouse Model

Statistical Analysis

Conclusions