Sargassum horneri (Turner) C. Agardh containing polyphenols attenuates particulate matter-induced inflammatory response by blocking TLR-mediated MYD88-dependent MAPK signaling pathway in MLE-12 cells

Abstract

Ethnopharmacological relevanceSargassum horneri (Turner) C. Agardh (S. horneri), an edible brown marine algae, is known to have immunomodulatory effects and has been used in oriental medicine to treat inflammatory diseases. It is well known that ambient particulate matter (PM) is closely related to increased respiratory diseases inducing lung inflammation. AimConsidering the use of Sargassum horneri in traditional medicine to treat inflammatory diseases, we hypothesized and investigated the use of Sargassum horneri containing polyphenols against PM-induced inflammatory responses. Materials and methodsIn this study, we evaluated the impact of PM (majority <2.5 μm in diameter) on deep bronchial penetration ability upon inhalation and a therapeutic approach to mitigate its harmful effects using an ethanol extract of Sargassum horneri, an edible brown algae, containing polyphenols on a type II alveolar epithelial cell line, MLE-12. ResultsPM triggered mRNA expression of toll-like receptors (TLRs) TLR2/4/7, and those TLRs were significantly attenuated by Sargassum horneri extract (SHE). SHE further attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase 1/2 (Erk1/2), and c-Jun NH (2)-terminal kinase (JNK), which were also activated in PM-exposed cells. Altogether, SHE subdued the PM-induced mRNA expression of pro-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6) and lung epithelial cell derived-chemokines (IL-8, monocyte chemoattractant protein-1 (MCP-1), and chemokine (C–C motif) ligand 5 (CCL5)). SHE also suppressed the mRNA expression of PM-induced pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33. Furthermore, we showed that SHE suppressed the MAPK-dependent signaling pathway by attenuating receptor-associated factor (TRAF) 6 activation of proteins MyD88 and TNF. ConclusionTaking all the data together, we suggest that the anti-inflammatory potential of SHE on PM-exposed MLE-12 cells is mediated by the inhibition of PM-triggered downstream signaling along the TLR2/4/7–MyD88–TRAF6 axis of MAPK signaling.