{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:09:40Z","timestamp":1787184580420,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,4,18]],"date-time":"2013-04-18T00:00:00Z","timestamp":1366243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Airway smooth muscle cells (ASMCs) participate in tissue remodeling characteristic of airway inflammatory diseases like asthma. Inflammation and hypoxia pathways are often interconnected and the regulatory subunit of the hypoxia inducible factor, HIF\u20101\u03b1, has been recently shown to be induced by cytokines. Here we investigate the effect of individual or combined treatment of ASMCs with the inflammatory mediator TNF\u03b1 and\/or hypoxia on the expression of HIF\u20101\u03b1, HIF\u20101 targets and inflammation markers. TNF\u03b1 enhances HIF\u20101\u03b1 protein and mRNA levels, under both normoxia and hypoxia. TNF\u03b1\u2010mediated induction of <jats:italic>HIF\u20101\u03b1<\/jats:italic> gene transcription is repressed by inhibition of the NF\u2010\u03baB pathway. Despite the up\u2010regulation of HIF\u20101\u03b1 protein, the transcription of HIF\u20101 target genes remains low in the presence of TNF\u03b1 at normoxia and is even reduced at hypoxia. We show that the reduction in HIF\u20101 transcriptional activity by TNF\u03b1 is due to inhibition of the interaction of HIF\u20101\u03b1 with ARNT and subsequent blocking of its binding to HREs. Comparison between hypoxia and TNF\u03b1 for their effects on the expression of inflammatory markers shows significant differences: hypoxia up\u2010regulates the expression of IL\u20106, but not RANTES or ICAM, and reduces the induction of VCAM by TNF\u03b1. Finally, ex vivo treatment of rabbit trachea strips with TNF\u03b1 increases HIF\u20101\u03b1 protein levels, but reduces the expression of HIF\u20101 targets under hypoxia. Overall, TNF\u03b1 induces HIF\u20101\u03b1 mRNA synthesis via an NF\u2010\u03baB dependent pathway but inhibits binding of HIF\u20101\u03b1 to ARNT and DNA, while hypoxia and TNF\u03b1 have distinct effects on ASMC inflammatory gene expression. J. Cell. Physiol. 228: 1745\u20131753, 2013. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.24331","type":"journal-article","created":{"date-parts":[[2013,1,28]],"date-time":"2013-01-28T14:34:08Z","timestamp":1359383648000},"page":"1745-1753","source":"Crossref","is-referenced-by-count":33,"title":["TNF\u03b1 induces expression of HIF\u20101\u03b1 mRNA and protein but inhibits hypoxic stimulation of HIF\u20101 transcriptional activity in airway smooth muscle cells"],"prefix":"10.1002","volume":"228","author":[{"given":"Stamatina","family":"Tsapournioti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Mylonis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolia","family":"Hatziefthimiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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