Etanercept attenuates short-term cigarette-smoke-exposure-induced pulmonary arterial remodelling in rats by suppressing the activation of TNF-α/NF-κB signal and the activities of MMP-2 and MMP-9

摘要

The pathogenesis of cigarette-smoke-exposure-induced pulmonary vasculature impairment is unclear. Cigarette-smoke-exposure-induced the accumulation of tumour necrosis factor-alpha (TNF-α) and up-regulates the expression and activities of matrix metalloproteinases (MMPs) involved in smoke-induced vascular remodelling, which are important processes in the pathogenesis of vasculature impairment. The TNF-α antagonist Etanercept is an anti-inflammatory drug with a potential role in regulating MMP expression. To determine the effect of Etanercept on short-term smoke-induced pulmonary arteriole impairment and investigate its possible mechanism, male Sprague-Dawley rats were exposed to cigarette-smoke daily for two weeks in both the absence and presence of Etanercept. Cigarette-smoke-exposure-induced elevation of mean pulmonary artery pressures and medial hypertrophy of pulmonary arterioles were partially reduced by Etanercept. Up-regulation of the expression and activities of MMP-2 and MMP-9, induced by cigarette-smoke, were also suppressed significantly by Etanercept. Furthermore, Etanercept treatment significantly attenuated cigarette-smoke-induced TNF-α accumulation and activation of nuclear factor NF-κB signal. These results suggest that Etanercept have the protective effects in cigarette-smoke-induced pulmonary vascular remodelling, with the attenuation of the up-regulated expression and activities of MMP-2 and MMP-9 and activation of TNF-α/NF-κB signal pathway probably being involved as part of its mechanism. Our study might provide insight into the development of new interventions for vasculature impairment.