| First Author | Kang MJ | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 3 | Pages | 1948-59 |
| PubMed ID | 17237446 | Mgi Jnum | J:143631 |
| Mgi Id | MGI:3828351 | Doi | 10.4049/jimmunol.178.3.1948 |
| Citation | Kang MJ, et al. (2007) IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation. J Immunol 178(3):1948-59 |
| abstractText | Th1 inflammation and remodeling characterized by local tissue destruction coexist in pulmonary emphysema and other diseases. To test the hypothesis that IL-18 plays an important role in these responses, we characterized the regulation of IL-18 in lungs from cigarette smoke (CS) and room air-exposed mice and characterized the effects of CS in wild-type mice and mice with null mutations of IL-18Ralpha (IL-18Ralpha(-/-)). CS was a potent stimulator and activator of IL-18 and caspases 1 and 11. In addition, although CS caused inflammation and emphysema in wild-type mice, both of these responses were significantly decreased in IL-18Ralpha(-/-) animals. CS also induced epithelial apoptosis, activated effector caspases and stimulated proteases and chemokines via IL-18Ralpha-dependent pathways. Importantly, the levels of IL-18 and its targets, cathepsins S and B, were increased in pulmonary macrophages from smokers and patients with chronic obstructive lung disease. Elevated levels of circulating IL-18 were also seen in patients with chronic obstructive lung disease. These studies demonstrate that IL-18 and the IL-18 pathway are activated in CS-exposed mice and man. They also demonstrate, in a murine modeling system, that IL-18R signaling plays a critical role in the pathogenesis of CS-induced inflammation and emphysema. |
