Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB pathway

Abstract

Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureusinduced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation. Furthermore, PD treatment dose-dependently decreased the levels of TNF-α, IL-1β, IL-6 and IL-8 in the mammary gland tissues. PD treatment also dose-dependently decreased the expression of TLR2, MyD88, IRAK1, IRAK4 and TRAF6 as well as the phosphorylation of TAK1, MKK3/6, p38 MAPK, IκB-α and NF-κB in the mammary gland tissues. In mouse mammary epithelial cells (mMECs) infected by S aureus in vitro, pretreatment with PD dose-dependently suppressed the upregulated pro-inflammatory cytokines and signaling proteins, and the nuclear translocation of NF-κB p65 and AP-1. A TLR2-neutralizing antibody mimicked PD in its suppression on S aureus-induced upregulation of MyD88, p-p38 and p-p65 levels in mMECs. PD (50, 100 μg/mL) affected neither the growth of S aureus in vitro, nor the viability of mMECs. In conclusion, PD does not exhibit antibacterial activity against S aureus, its therapeutic effects in mouse S aureus-induced mastitis depend on its ability to down-regulate pro-inflammatory cytokine levels via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB signaling pathway.

Gefitinib Inhibits Bleomycin‐Induced Pulmonary Fibrosis via Alleviating the Oxidative Damage in Mice

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Polydatin reduces Staphylococcus aureus lipoteichoic acid‐induced injury by attenuating reactive oxygen species generation and TLR2‐NFκB signalling

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miR‐148a suppresses inflammation in lipopolysaccharide‐induced endometritis

“…qPCR and Western blot were carried out according to the manufacturer's instructions as previously reported . qPCR was performed using SYBR Premix DimerEraser (Takara) on a 7900HT system.…”

“…qPCR and Western blot were carried out according to the manufacturer's instructions as previously reported. 31 qPCR was performed using SYBR Premix DimerEraser (Takara) on a 7900HT system. The relative expression of miR-148a and specific mRNAs was normalized against internal controls (U6 or GAPDH) using the 2 −ΔΔCt method.…”