{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:24:03Z","timestamp":1789619043930,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673747"],"award-info":[{"award-number":["81673747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603447"],"award-info":[{"award-number":["81603447"]}],"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":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aim of this study was to identify the association polymorphism (rs11536889) in the 3\u2032\u2010untranslated region (3\u2032\u2010UTR) of Toll\u2010like receptors 4 (TLR4) and the risk for ventilator\u2010associated pneumonia (VAP). miRNA database online and luciferase assays were used to validate TLR4 as the target gene of miR\u20101236. Enzyme\u2010linked immunosorbent assay analysis and western blot were used to analyze the level of TLR4 in different genotype groups. In the present study, miR\u20101236 was predicted to bind to the rs11536889 G allele rather than the rs11536889 C allele, which was further confirmed by the luciferase activity suppressed by a fragment of 3\u2032\u2010UTR containing the rs11536889 G allele induced by lipopolysaccharide (LPS) and interleukin\u20106 (IL\u20106). Bronchial epithelial cells isolated from participants genotyped as GG, GC, and CC, with no remarkable difference in TLR4 messenger RNA (mRNA) levels were observed among these genotype groups. After stimulating by LPS, a TLR4 ligand, the CC\u2010genotyped cells expressed higher levels of IL\u20108, IL\u20106, and tumor necrosis factor alpha (TNF\u2010\u03b1) on their surfaces than cells with the other genotypes. Finally, the western blot analysis results showed that the expression level of IL\u20108, IL\u20106, and TNF\u2010\u03b1 protein was much higher in the CC group than the GC and GG groups subsequent to stimulation\u00a0by LPS, and the IL\u20108, IL\u20106, and TNF\u2010\u03b1 protein levels in the GC were grouped much lower compared\u00a0with the GG group. These findings indicated the regulatory association of miR\u20101236 with TLR4 and the abnormal expression of TLR4 caused by the presence of rs11536889 in the 3\u2032\u2010UTR of mRNA, which interfere with its interaction with the miR\u20101236, contributing\u00a0to the risk of VAP.<\/jats:p>","DOI":"10.1002\/jcp.28526","type":"journal-article","created":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T17:49:52Z","timestamp":1555004992000},"page":"18879-18886","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["One functional variant in the 3\u2032\u2010untranslated region of TLR4 is associated with the elevated risk of ventilator\u2010associated pneumonia in the patients with chronic obstructive pulmonary disease"],"prefix":"10.1002","volume":"234","author":[{"given":"Xiaoyun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Tianjin Chest Hospital 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