{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:05:17Z","timestamp":1782421517227,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001590","name":"Health Research Board","doi-asserted-by":"publisher","award":["EIA\u20102017\u2010034"],"award-info":[{"award-number":["EIA\u20102017\u2010034"]}],"id":[{"id":"10.13039\/501100001590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intermittent hypoxia (IH) plays a key role in the pathogenesis of insulin resistance (IR) in obstructive sleep apnoea (OSA). IH induces a pro\u2010inflammatory phenotype of the adipose tissue with M1 macrophage polarisation, subsequently impeding adipocyte insulin signalling, and these changes are in striking similarity to those seen in obesity. However, the detailed molecular mechanisms of IH\u2010induced macrophage polarisation are unknown and identification of same should lead to the identification of novel therapeutic targets. In the present study, we tested the hypothesis that IH acts through similar mechanisms as obesity, activating Toll\u2010like\u2010receptor (TLR)4\/nuclear factor \u03ba\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) and nucleotide\u2010binding domain (NOD)\u2010like receptor protein 3 (NLRP3) signalling pathways leading to the upregulation and secretion of the key cytokines interleukin (IL)\u20101\u03b2 and IL\u20106. Bone\u2010marrow derived macrophages (BMDMs) from lean and obese C57BL\/6 male mice were exposed to a state\u2010of\u2010the\u2010art in vitro model of IH. Independent of obesity, IH led to a pro\u2010inflammatory M1 phenotype characterised by increased inducible nitric oxide synthase and IL\u20106 mRNA expression, robust increase in NF\u2010\u03baB DNA\u2010binding activity and IL\u20106 secretion. Furthermore, IH significantly increased pro\u2010IL\u20101\u03b2 mRNA and protein expression and mature IL\u20101\u03b2 secretion compared to control treatment. Providing mechanistic insight, pre\u2010treatment with the TLR4 specific inhibitor, TAK\u2010242, prevented IH\u2010induced M1 polarisation and upregulation of IL\u20101\u03b2 mRNA and pro\u2010IL\u20101\u03b2 protein expression. Moreover, IH\u2010induced increase in IL\u20101\u03b2 secretion was prevented in BMDMs isolated from NLRP3 knockout mice. Thus, targeting TLR4\/NF\u2010\u03baB and NLRP3 signalling pathways may provide novel therapeutic options for metabolic complications in OSA.<\/jats:p>","DOI":"10.1111\/jsr.13202","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T10:44:14Z","timestamp":1601462654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Mechanisms of intermittent hypoxia\u2010mediated macrophage activation \u2013 potential therapeutic targets for obstructive sleep apnoea"],"prefix":"10.1111","volume":"30","author":[{"given":"Susan F.","family":"Fitzpatrick","sequence":"first","affiliation":[{"name":"School of Medicine Conway Institute University College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailbhe D.","family":"King","sequence":"additional","affiliation":[{"name":"School of Medicine Conway Institute University College Dublin Dublin 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