Cigarette smoke as a trigger for the dioxin receptor-mediated signaling pathway

Dioxins and dioxin-like chemicals cause a wide range of pathologies including carcinogenesis, immune dysfunction, and developmental/reproductive abnormalities. Most of these toxic effects are mediated by aryl hydrocarbon receptor (AhR; also called the dioxin receptor), a ligand-activated transcription factor. Constitutive activation of AhR via genetic manipulation causes development of cancers, inflammation and immune abnormality in mice even without exposure to xenobiotic ligands. Recent investigation disclosed that cigarette smoke contains high levels of agonists for AhR and strongly activates the dioxin signaling pathway. In this review, we describe and discuss possible roles of AhR activation in cigarette smoke-related pathologies, especially focusing on carcinogenesis, inflammation, atherosclerosis, immune dysfunction and teratogenesis.