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Here, we report that knocking out miR\u2010144\/451 in mice exacerbates lipopolysaccharide (LPS)\u2010induced lung inflammation. The lung inflammation in mice was induced by intratracheal instillation of LPS. Loss\u2010of\u2010function experiments demonstrated that miR\u2010144\/451 gene knockout (KO) increased LPS\u2010induced lung inflammation and oxidant stress compared with wild\u2010type (WT) mice, as manifested by increased total bronchoalveolar lavage fluid cells and neutrophil counts, elevated TNF\u2010\u03b1 and IL\u20106 levels in bronchoalveolar lavage fluid, enhanced myeloperoxidase activity, and reduced catalase and glutathione peroxidase activity in lung tissues. We also found that LPS significantly decreased miR\u2010451 expression in lung tissues and macrophages; while miR\u2010451 overexpression in LPS\u2010induced RAW264.7 cells remarkably reduced TNF\u2010\u03b1 and IL\u20106 levels as well as reactive oxygen species (ROS) production, suggesting a feedback loop might exist in inflammatory cells. Rac1 mRNA and protein levels were downregulated in miR\u2010451\u2010overexpressed RAW264.7 cells. Ex vivo stimulation experiments, performed using alveolar macrophages isolated from miR\u2010144\/451 KO mice, confirmed that Rac1 inhibitor alleviated levels of TNF\u2010\u03b1 and ROS in response to LPS stimulation compared with WT controls. Luciferase reporter assay demonstrated that STAT\u20103 is a direct target of miR\u2010451. STAT\u20103 protein levels were elevated in miR\u2010144\/451 KO macrophages. LPS treatment also resulted in higher phosphorylation levels of STAT\u20103 in macrophages from KO mice than in WT cells. Our study identified miR\u2010144\/451 as an anti\u2010inflammatory factor in LPS\u2010induced lung inflammation that acts by downregulating Rac1 and STAT\u20103.<\/jats:p>","DOI":"10.1002\/jbt.70006","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T18:54:35Z","timestamp":1730141675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["MiR\u2010144\/451 attenuates lipopolysaccharide\u2010induced lung inflammation by downregulating Rac1 and STAT\u20103 in macrophages"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5531-714X","authenticated-orcid":false,"given":"Sheng","family":"He","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Basic Research on Prevention and Control of Birth Defects and Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang 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