| Toll-Like Receptor 4 and MYD88-Dependent Signaling Mechanisms of the Innate Immune System Are Essential for the Response to Lipopolysaccharide by Epithelial and Stromal Cells of the Bovine Endometrium. | |
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MedLine Citation:
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PMID: 22053092 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Infection of the bovine endometrium with Gram-negative bacteria commonly causes uterine disease. Toll-like receptor 4 (TLR4) on cells of the immune system bind Gram-negative bacterial lipopolysaccharide (LPS), stimulating the secretion of the pro-inflammatory cytokines interleukin (IL) 1B and IL6, and the chemokine IL8. As the endometrium is the first barrier to infection of the uterus, the signaling cascade triggered by LPS and the subsequent expression of inflammatory mediators was investigated in endometrial epithelial and stromal cells, and the key pathways identified using short interfering RNA (siRNA) and biochemical inhibitors. Treatment of endometrial cells with ultrapure LPS stimulated an inflammatory response characterized by increased IL1B, IL6, and IL8 mRNA expression, and IL6 protein accumulation in epithelial cells; and increased IL1B and IL8 mRNA expression, and IL6 and IL8 protein accumulation in stromal cells. Treatment of endometrial cells with LPS also induced the degradation of IKB and the nuclear translocation of NFKB, as well as rapid phosphorylation of MAPK3/1 and MAPK14. Knockdown of TLR4 or its signaling adaptor molecule, MYD88, using siRNA reduced the inflammatory response to LPS in epithelial and stromal cells. Biochemical inhibition of MAPK3/1, but not JNK, or MAPK14, reduced LPS-induced IL1B, IL6 and IL8 expression in endometrial cells. In conclusion, epithelial and stromal cells have an intrinsic role in innate immune surveillance in the endometrium, and in the case of LPS this recognition occurs via TLR4 and MYD88 dependent cell signaling pathways. |
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Authors:
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James G Cronin; Matthew L Turner; Leopold Goetze; Clare E Bryant; I Martin Sheldon |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-2 |
Journal Detail:
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Title: Biology of reproduction Volume: - ISSN: 1529-7268 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0207224 Medline TA: Biol Reprod Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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