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Progesterone elicits immunosuppressive function within bovine endometrium, and has been suggested to be related to postpartum uterine infection. Endometrial stroma is exposed to bacteria due to the disruption of epithelium during parturition, but the effect and mechanism of progesterone on innate immune response of stromal cells has not been reported. This study evaluated the impact of progesterone on inflammatory response of primary endometrial stromal cells stimulated by lipopolysaccharide or heat-killed <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>. Quantitative PCR analysis revealed that progesterone repressed mRNA induction of <jats:italic>IL1B<\/jats:italic>, <jats:italic>IL6<\/jats:italic>, <jats:italic>TNF<\/jats:italic>, <jats:italic>CXCL8<\/jats:italic>, <jats:italic>NOS2<\/jats:italic>, and <jats:italic>PTGS2<\/jats:italic> in stromal cells in response to lipopolysaccharide or <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> challenge. Consistently, Western blot and immunofluorescence staining results showed that progesterone suppressed lipopolysaccharide- or <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>-induced MAPK and NF-\u03baB activations characterized with decreased phosphorylations of ERK1\/2, JNK, P38, I\u03baB\u03b1, and P65, and inhibition of P65 nuclear translocation. In unstimulated stromal cells, progesterone alone did not affect the mRNA transcription for <jats:italic>IL6<\/jats:italic>, <jats:italic>TNF<\/jats:italic>, <jats:italic>CXCL8<\/jats:italic>, <jats:italic>NOS2<\/jats:italic>, and <jats:italic>PTGS2<\/jats:italic>, and the signaling cascade of MAPK and NF-\u03baB, but decreased <jats:italic>IL1B<\/jats:italic> mRNA expression. These results revealed that the anti-inflammatory effect of progesterone in lipopolysaccharide- or <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>-challenged endometrial stromal cells was probably mediated through MAPK and NF-\u03baB pathways.<\/jats:p>","DOI":"10.1371\/journal.pone.0266144","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T17:30:03Z","timestamp":1651080603000},"page":"e0266144","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Anti-inflammatory effects of progesterone through NF-\u03baB and MAPK pathway in lipopolysaccharide- or Escherichia coli-stimulated bovine endometrial stromal cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Luying","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenye","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangling","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsheng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-5921","authenticated-orcid":true,"given":"Jianji","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"pone.0266144.ref001","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.anireprosci.2004.04.006","article-title":"Postpartum 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