{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:35:02Z","timestamp":1787870102783,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31800988"],"award-info":[{"award-number":["31800988"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Evidence indicates that inflammatory response is significant during the physiological process of human parturition; however, the specific signaling pathway that triggers inflammation is undefined. Toll\u2010like receptors (TLRs) are key upstream gatekeepers that control inflammatory activation before preterm delivery. Our previous study showed that TLR4 expression was significantly increased in human pregnancy tissue during preterm and term labor. Therefore, we explore whether TLR4 plays a role in term labor by initiating inflammatory responses, therefore promoting uterine activation. The results showed that expression of TLR4, interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), CC chemokine ligand 2 (CCL\u20102), and uterine contraction\u2010associated proteins (CAPs) was upregulated in the human and mice term labor (TL) group compared with the not\u2010in\u2010labor (TNL) group, and the TLR4 level positively correlated with CAP expression. In pregnant TLR4\u2010knockout (TLR4<jats:sup>\u2212\/\u2212<\/jats:sup>) mice, gestation length was extended by 8\u2009hr compared with the wild\u2010type group, and the expression of IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, CCL\u20102, and CAPs was decreased in TLR4<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Furthermore, nuclear factor\u2010\u03baB (NF\u2010\u03baB) and P38MAPK activation is involved in the initiation of labor but was inhibited in TLR4<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In uterine smooth muscle cells, the expression of inflammatory cytokines and CAPs decreased when the NF\u2010\u03baB and P38MAPK pathway was inhibited. Our data suggest that TLR4 is a key factor in regulating the inflammatory response that drives uterine activation and delivery initiation via activating the NF\u2010\u03baB\/P38MAPK pathway.<\/jats:p>","DOI":"10.1002\/jcp.28991","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T18:31:14Z","timestamp":1561487474000},"page":"513-525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Toll\u2010like receptor 4 contributes to uterine activation by upregulating pro\u2010inflammatory cytokine and CAP expression via the NF\u2010\u03baB\/P38MAPK signaling pathway during pregnancy"],"prefix":"10.1002","volume":"235","author":[{"given":"Zixi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Putuo Hospital Shanghai University of Traditional Chinese Medicine Shanghai 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