Acute inflammation induces insulin-like growth factor-1 to mediate Bcl-2 and Muc5ac expression in airway epithelial cells.

Generally, exposure to LPS in human airways occurs in the form of aerosols and causes an acute inflammatory response or exacerbates existing chronic inflammatory conditions by enhancing airway remodeling and associated pathologies. The present study evaluated which inflammatory mediators may be responsible for the expression of Bcl-2 and mucus cell metaplasia when mice are exposed to aerosolized LPS. At 3 days after exposure, aerosolized LPS (for 20-40 min) with the estimated lung deposited dosage of 0, 0.02, 0.2, 1.4, and 20.2 μg showed a characteristic dose-dependent increase in polymorphonuclear neutrophils. Significant increases of proinflammatory mediators, including IL-1β, TNF-α, IL-6, growth-related oncogene or keratinocyte-derived cytokine, IFN-γ-induced protein-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α, were detected at the highest doses. In addition to increased numbers of airway epithelial cells, mucus cell numbers and mucus production were increased in a dose-dependent manner. Hyperplastic epithelial cells expressed insulin-like growth factor (IGF)-1 and, similar to previous studies, increased expression of the prosurvival protein Bcl-2 and induced expression of Muc5ac. Suppression of IGF-1 expression using retroviral shRNA blocked Bcl-2 expression in human and murine airway epithelial cells and Muc5ac in primary murine airway epithelial cells. These findings show that acute inflammation induces IGF-1 to mediate Bcl-2 and Muc5ac expression in airway epithelial cells.