IL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation

摘要: Th1 inflammation and remodeling characterized by local tissue destruction coexist in pulmonary emphysema other diseases. To test the hypothesis that IL-18 plays an important role these responses, we regulation of lungs from cigarette smoke (CS) room air-exposed mice effects CS wild-type with null mutations IL-18Rα (IL-18Rα−/−). was a potent stimulator activator caspases 1 11. In addition, although caused mice, both responses were significantly decreased IL-18Rα−/− animals. also induced epithelial apoptosis, activated effector stimulated proteases chemokines via IL-18Rα-dependent pathways. Importantly, levels its targets, cathepsins S B, increased macrophages smokers patients chronic obstructive lung disease. Elevated circulating seen These studies demonstrate pathway are CS-exposed man. They demonstrate, murine modeling system, IL-18R signaling critical pathogenesis CS-induced emphysema.