Resistin Deficiency In Mice Has No Effect On Pulmonary Responses Induced By Acute Ozone Exposure

Acute exposure to ozone (O-3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1 alpha and IL-1 beta)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1 alpha, IL-1 beta, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O-3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O-3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O-3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O-3 increased lung tissue or BALF IL-1 alpha, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O-3 exposure. O-3 caused AHR to acetyl-beta-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O-3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O-3 exposure but does not promote O-3-induced lung pathology.