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Concentrated Ambient PM<subscript>2.5</subscript>-Induced Inflammation and Endothelial Dysfunction in a Murine Model of Neural IKK2 Deficiency.
In: Environmental Health Perspectives, Jg. 126 (2018-02-01), Heft 2, S. 1-10
Online
academicJournal
Zugriff:
BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with cardiovascular mortality, but underlying pathophysiologic mechanisms are not fully understood. Hypothalamic inflammation, characterized by the activation of Inhibitor kappaB kinase 2/Nuclear factor kappaB (IKK2/NF-κB) signaling pathway, may play an important role in the pathogenesis of cardiovascular diseases. We recently demonstrated that hypothalamic inflammation is increased in mice exposed to concentrated ambient PM2.5 (CAP). OBJECTIVES: In the present study, we used a neuron-specific IKK2 knockout mouse model to examine the role of neural IKK2 expression and hypothalamic inflammation in the pathophysiologic effects of PM2.5. METHODS: We assessed inflammatory and vascular responses in Nestin-creIKK2flox/flox (IKK2Neu-KO) and littermate Nestin-creIKK2flox/+ (control) mice after 4 mo of exposure to filtered air (FA) or CAP. RESULTS: CAP exposure was associated with significantly higher tumor necrosis factor-α (TNFα) and interleukin (IL)-6 mRNA in the hypothalamus of control mice, but not IKK2Neu-KO mice. In addition, CAP exposure-induced increases in bronchoalveolar lavage fluid (BALF) leukocytes, pulmonary macrophage infiltration and IL-6 expression, plasma TNFα and IL-1β levels, adipose macrophage infiltration and IL-1β expression, and endothelial dysfunction were reduced or absent in IKK2Neu-KO mice compared with controls. CONCLUSIONS: Our findings support a role of neural IKK2 in CAP exposure-induced local and systemic pro-inflammatory cytokine expression, pulmonary and adipose inflammation, and endothelial dysfunction, thus providing insight into pathophysiologic mechanisms that may mediate effects of PM2.5 exposure. [ABSTRACT FROM AUTHOR]
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Concentrated Ambient PM<subscript>2.5</subscript>-Induced Inflammation and Endothelial Dysfunction in a Murine Model of Neural IKK2 Deficiency.
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Autor/in / Beteiligte Person: | Chen, Minjie ; Qin, Xiaobo ; Qiu, Lianglin ; Chen, Sufang ; Zhou, Huifen ; Xu, Yanyi ; Hu, Ziying ; Zhang, Yuhao ; Cao, Qi ; Ying, Zhekang |
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Zeitschrift: | Environmental Health Perspectives, Jg. 126 (2018-02-01), Heft 2, S. 1-10 |
Veröffentlichung: | 2018 |
Medientyp: | academicJournal |
ISSN: | 0091-6765 (print) |
DOI: | 10.1289/EHP2311 |
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