TY - JOUR T1 - Cigarette Smoke Activates Human Monocytes by an Oxidant-AP-1 Signaling Pathway: Implications for Steroid Resistance JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1343 LP - 1353 DO - 10.1124/mol.105.012591 VL - 68 IS - 5 AU - Matthew J. Walters AU - Mark J. Paul-Clark AU - Shaun K. McMaster AU - Kazuhiro Ito AU - Ian M. Adcock AU - Jane A. Mitchell Y1 - 2005/11/01 UR - http://molpharm.aspetjournals.org/content/68/5/1343.abstract N2 - 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-1β and tumor necrosis factor-α, 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 κB, 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. ER -