Etanercept attenuates short-term cigarette-smoke-exposure-induced pulmonary arterial remodelling in rats by suppressing the activation of TNF-a/NF-kB signal and the activities of MMP-2 and MMP-9.
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 upregulates 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 TNFα accumulation and activation of nuclear factor NF-kB 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-kB signal pathway probably being involved as part of its mechanism. Our study might provide insight into the development of new interventions for vasculature impairment.
Department of respiratory medicine, The First Affiliated Hospital of Nanjing Medical University, and Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing, Jiangsu, PR China. hong_xue1987@yahoo.com.cn
Hong
H
Xue
Kai
K
Sun
Weiping
W
Xie
Gang
G
Hu
Hui
H
Kong
Qiang
Q
Wang
Hong
H
Wang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000068800:Etanercept