Walters Matthew J, Paul-Clark Mark J, McMaster Shaun K, Ito Kazuhiro, Adcock Ian M, Mitchell Jane A
Cardiothoracic Pharmacology, Unit of Critical Care Medicine, Imperial College London, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, UK.
Mol Pharmacol. 2005 Nov;68(5):1343-53. doi: 10.1124/mol.105.012591. Epub 2005 Aug 1.
Smoking cigarettes is a major risk factor for the development of cardiovascular and respiratory disease. Moreover, smoking-induced pathophysiology is often resistant to the anti-inflammatory effects of glucocorticoids. The nature of cigarette smoke-induced inflammation is still not defined, although neutrophil recruitment and activation seem to be consistent features. In the current study, we have used a range of approaches to demonstrate that cigarette smoke activates human monocytes and macrophages to release the CXC chemokine CXCL8 [(interleukin-8 (IL-8)]. Furthermore, we show for the first time that cigarette smoke synergizes with proinflammatory cytokines IL-1beta and tumor necrosis factor-alpha, and it is this interaction that confers steroid resistance to smoke-induced CXCL8 release. We go on to show that smoke-induced activation of human cells is an oxidant-mediated phenomenon acting through activator protein-1, but not nuclear factor kappaB, pathway. These observations add significantly to our understanding of smoke as an inflammatory stimulus that has implications for potential the development of treatments of smoking or related disease.
吸烟是心血管疾病和呼吸系统疾病发生的主要危险因素。此外，吸烟引起的病理生理学通常对糖皮质激素的抗炎作用具有抗性。尽管中性粒细胞的募集和激活似乎是一致的特征，但香烟烟雾引起的炎症性质仍未明确。在当前的研究中，我们使用了一系列方法来证明香烟烟雾可激活人类单核细胞和巨噬细胞，使其释放CXC趋化因子CXCL8 [白细胞介素-8 (IL-8)]。此外，我们首次表明香烟烟雾与促炎细胞因子IL-1β和肿瘤坏死因子-α协同作用，正是这种相互作用赋予了对烟雾诱导的CXCL8释放的类固醇抗性。我们接着表明，烟雾诱导的人类细胞激活是一种通过激活蛋白-1而非核因子κB途径介导的氧化现象。这些观察结果显著增进了我们对烟雾作为一种炎症刺激物的理解，这对吸烟或相关疾病潜在治疗方法的开发具有重要意义。
