<p><i>Streptococcus equi</i> subsp. <i>zooepidemicus</i> (SEZ) is an important zoonotic pathogen that causes severe inflammatory diseases in various animal species. The host inflammatory response is a key factor in SEZ pathogenesis, yet the regulatory role of microRNAs (miRNAs) in this process remains largely unexplored. In this study, we investigated the function of miR-7002-5p in SEZ-induced inflammation using murine macrophage J774A.1 cells and C57BL/6J mice. SEZ infection led to a significant downregulation of miR-7002-5p and upregulation of inflammatory cytokines. Bioinformatics prediction and dual-luciferase reporter assays confirmed that Caspase-1 is a direct target of miR-7002-5p. Overexpression of miR-7002-5p significantly suppressed Caspase-1 activation and reduced the expression of IL-1β, IL-18, IL-6, and TNF-α both in vitro and in vivo. In contrast, inhibition of miR-7002-5p exacerbated inflammatory responses. Furthermore, intranasal delivery of miR-7002-5p mimics in SEZ-infected mice alleviated lung inflammation, as evidenced by reduced cytokine levels and histopathological improvement. These findings suggest that miR-7002-5p mitigates SEZ-induced inflammation by targeting Caspase-1 and may serve as a potential therapeutic target for controlling SEZ infection.</p>

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miR-7002-5p targets caspase-1 to suppress the inflammatory response of macrophages induced by Streptococcus equi subsp. zooepidemicus

  • Honglin Xie,
  • Jingfei Deng,
  • Jingyu Yu,
  • Shun Li,
  • Yibo Wang,
  • Yajuan Li,
  • Yunfei Huang,
  • Qinqin Sun,
  • Jiedan Liao,
  • Ziteng Deng,
  • Qiang Fu

摘要

Streptococcus equi subsp. zooepidemicus (SEZ) is an important zoonotic pathogen that causes severe inflammatory diseases in various animal species. The host inflammatory response is a key factor in SEZ pathogenesis, yet the regulatory role of microRNAs (miRNAs) in this process remains largely unexplored. In this study, we investigated the function of miR-7002-5p in SEZ-induced inflammation using murine macrophage J774A.1 cells and C57BL/6J mice. SEZ infection led to a significant downregulation of miR-7002-5p and upregulation of inflammatory cytokines. Bioinformatics prediction and dual-luciferase reporter assays confirmed that Caspase-1 is a direct target of miR-7002-5p. Overexpression of miR-7002-5p significantly suppressed Caspase-1 activation and reduced the expression of IL-1β, IL-18, IL-6, and TNF-α both in vitro and in vivo. In contrast, inhibition of miR-7002-5p exacerbated inflammatory responses. Furthermore, intranasal delivery of miR-7002-5p mimics in SEZ-infected mice alleviated lung inflammation, as evidenced by reduced cytokine levels and histopathological improvement. These findings suggest that miR-7002-5p mitigates SEZ-induced inflammation by targeting Caspase-1 and may serve as a potential therapeutic target for controlling SEZ infection.