资源环境科技发展态势分析平台

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-kappa B) 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-creIKK2(flox/flox) (IKK2(Nen-KO)) and littermate Nestin-creIKK2(flox/+) (control) mice after 4 mo of exposure to filtered air (FA) or CAP.

RESULTS: CAP exposure was associated with significantly higher tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-6 mRNA in the hypothalamus of control mice, but not IKK2(Nen-KO) mice. in addition, CAP exposure induced increases in bronchoalveolar lavage fluid (BALF) leukocytes, pulmonary macrophage infiltration and IL -6 expression, plasma TNF alpha and IL-1 beta levels, adipose macrophage infiltration and IL-1 beta expression, and endothelial dysfunction were reduced or absent in IKK2(Nen-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.