Investigating the role of the mPGES-PGE2-EP4 pathway in Escherichia coli-induced mastitis in dairy cows: insights for non-antibiotic therapeutic strategies

文献类型： 外文期刊

第一作者： Yang, Xiaolin

作者： Yang, Xiaolin;Li, Xueqiang;Guo, Lili;Gong, Pengfei;Zhang, Shuangyi;Liu, Bo;Guo, Wenrui;Bao, Haixia;Mao, Wei;Yang, Xiaolin;Li, Xueqiang;Guo, Lili;Gong, Pengfei;Zhang, Shuangyi;Liu, Bo;Guo, Wenrui;Bao, Haixia;Mao, Wei;Gong, Pengfei;Qian, Yinghong

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关键词： Escherichia coli; mastitis; alternative treatments to antibiotics; mPGES-1 inhibitors; EP4 receptor inhibitor

期刊名称：FRONTIERS IN VETERINARY SCIENCE （ 影响因子：2.9； 五年影响因子：3.3 ）

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年卷期： 2025 年 12 卷

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收录情况： SCI

摘要： Escherichia coli (E. coli) is the primary causative agent of bovine mastitis. Currently, antibiotic therapy remains the cornerstone of mastitis treatment; necessitating the identification of alternative therapeutic options. This study employed in vitro cultured bovine bone marrow-derived macrophages (BMDMs) to systematically assess the potential of microsomal prostaglandin e synthase-1 (mPGES-1) inhibitors (MF63, MK886) and EP4 receptor inhibitor (Grapiprant) in modulating inflammatory responses and reducing tissue damage. Cells were pre-treated with mPGES-1 inhibitors and an EP4 receptor inhibitor before infection with E. coli. Following infection, extracellular bacteria were removed, and assays-including ELISA, Western blot, and qRT-PCR-were conducted to analyze inflammatory mediators, protein expression, and gene expression. E. coli infection significantly induced PGE(2) synthesis in BMDMs, which exacerbated the inflammatory response and tissue damage via NF-kappa B and MAPK signaling pathways, elevating TNF-alpha, IL-1 beta, IL-6, and IL-8. Treatment with MF63, MK886 and Grapiprant effectively reduced PGE(2) levels, inhibited NF-kappa B and MAPK signaling pathways, decreased inflammatory mediators, and enhanced macrophage bactericidal activity, thereby demonstrating potent anti-inflammatory and immunomodulatory effects. Moreover, inhibition of the mPGES-PGE(2)-EP4 signaling pathway was found to reduce the expression of damage-associated molecular patterns (HMGB-1 and HABP-2), suggesting alleviation of E. coli-induced tissue damage. Based on the role of PGE(2) in mediating immune and inflammatory responses via the EP4 receptor, inhibiting the mPGES-1-PGE(2)-EP4 signaling axis to reduce inflammation and tissue damage will facilitate further investigation into the regulatory mechanisms of the PGE(2) signaling axis in the pathogenesis of mastitis. This approach provides a theoretical foundation and experimental basis for the development of alternative anti-inflammatory therapies to replace antibiotics.

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