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dc.contributor.authorChen, S.
dc.contributor.authorChen, M.
dc.contributor.authorWei, W.
dc.date.accessioned2019-09-13T16:41:56Z
dc.date.available2019-09-13T16:41:56Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85066818951&doi=10.1289%2fEHP4591&partnerID=40&md5=fab8826e68b30373e995b348fae52ee9
dc.identifier.urihttp://hdl.handle.net/10713/10648
dc.description.abstractBackground: Pulmonary inflammation is believed to be central to the pathogenesis due to exposure to fine particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5). This central role, however, has not yet been systemically examined. Objective: In the present study, we exploited a lung epithelial cell-specific inhibitor κB kinase 2 (IKK2) knockout mouse model to determine the role of pulmonary inflammation in the pathophysiology due to exposure to diesel exhaust particulate matter (DEP). Methods: SFTPC-rtTA+/−tetO-cre+/−IKK2flox/flox (lung epithelial cell-specific IKK2 knockout, KO) and SFTPC-rtTA+/−tetO-cre+/−IKK2flox/flox (wild-type, tgWT) mice were intratracheally instilled with either vehicle or DEP for 4 months, and their inflammatory response and glucose homeostasis were then assessed. Results: In comparison with tgWT mice, lung epithelial cell-specific IKK2-deficient mice had fewer DEP exposure-induced bronchoalveolar lavage fluid immune cells and proinflammatory cytokines as well as fewer DEP exposure-induced circulating proinflammatory cytokines. Glucose and insulin tolerance tests revealed that lung epithelial cell-specific IKK2 deficiency resulted in markedly less DEP exposure–induced insulin resistance and greater glucose tolerance. Akt phosphorylation analyses of insulin-responsive tissues showed that DEP exposure primarily targeted hepatic insulin sensitivity. Lung epithelial cell–specific IKK2-deficient mice had significantly lower hepatic insulin resistance than tgWT mice had. Furthermore, this difference in insulin resistance was accompanied by consistent differences in hepatic insulin receptor substrate 1 serine phosphorylation and inflammatory marker expression. Discussion: Our findings suggest that in a tissue-specific knockout mouse model, an IKK2-dependent pulmonary inflammatory response was essential for the development of abnormal glucose homeostasis due to exposure to DEP. Copyright 2019, Public Health Services, US Dept of Health and Human Services. All rights reserved.en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (R01ES024516 to Z.Y.), the American Heart Association (13SDG17070131 to Z.Y.), the National Natural Science Foundation of China (81500216 to C.M.), the 2016 Henan Province Health System Abroad Training Project (2016011 to S. C.), and 2017 Henan Medical Science and Technology Research Project (201702050 to S.C.).en_US
dc.description.urihttps://doi.org/10.1289/EHP4591en_US
dc.language.isoen-USen_US
dc.publisherPublic Health Services, US Dept of Health and Human Servicesen_US
dc.relation.ispartofEnvironmental Health Perspectives
dc.subject.meshEpithelial Cellsen_US
dc.subject.meshInflammationen_US
dc.subject.meshLungen_US
dc.subject.meshParticulate Matter--adverse effectsen_US
dc.titleGlucose homeostasis following diesel exhaust particulate matter exposure in a lung epithelial cell-specific IKK2-deficient mouse modelen_US
dc.typeArticleen_US
dc.identifier.doi10.1289/EHP4591
dc.identifier.pmid31095431


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