Pulmonary Inflammation Induced by Subacute Ozone Is Augmented in Adiponectin-Deficient Mice: Role of IL-17A

Abstract

Pulmonary responses to ozone, a common air pollutant, are augmented in obese individuals. Adiponectin, an adipose-derived hormone that declines in obesity, has regulatory effects on the immune system. To determine the role of adiponectin in the pulmonary inflammation induced by extended (48–72 h) low-dose (0.3 parts per million) exposure to ozone, adiponectin-deficient (Adipo−/−) and wild-type mice were exposed to ozone or to room air. In wild-type mice, ozone exposure increased total bronchoalveolar lavage (BAL) adiponectin. Ozone-induced lung inflammation, including increases in BAL neutrophils, protein (an index of lung injury), IL-6, keratinocyte-derived chemokine, LPS-induced CXC chemokine, and G-CSF were augmented in Adipo−/− versus wild-type mice. Ozone also increased IL-17A mRNA expression to a greater extent in Adipo−/− versus wild-type mice. Moreover, compared with control Ab, anti–IL-17A Ab attenuated ozone-induced increases in BAL neutrophils and G-CSF in Adipo−/− but not in wild-type mice, suggesting that IL-17A, by promoting G-CSF release, contributed to augmented neutrophilia in Adipo−/− mice. Flow cytometric analysis of lung cells revealed that the number of CD45+/F4/80+/IL-17A+ macrophages and γδ T cells expressing IL-17A increased after ozone exposure in wild-type mice and further increased in Adipo−/− mice. The IL-17+ macrophages were CD11c− (interstitial macrophages), whereas CD11c+ macrophages (alveolar macrophages) did not express IL-17A. Taken together, the data are consistent with the hypothesis that adiponectin protects against neutrophil recruitment induced by extended low-dose ozone exposure by inhibiting the induction and/or recruitment of IL-17A in interstitial macrophages and/or γδ T cells.

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

“…In the mouse model of multiple sclerosis, which is another representative Th17-related disease, adiponectin-deficient mice developed worse experimental autoimmune encephalomyelitis with higher IL-17 expression of spinal cord tissues 49 . Another report can be obtained from an ozone-induced pulmonary inflammation model, one of the mouse models for asthma, in which adiponectin-deficient mice showed increased ozone-induced inflammation and IL-17A expression in the lung 50 . In the present study, adiponectindeficient mice developed worse psoriasis inflammation with increased IL-17 expression of the skin, strengthening the hypothesis that adiponectin possesses anti-inflammatory properties in the regulation of IL-17.…”

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

“…Several experimental studies in mice have identified augmented responses to ozone in obese animals (26,27). A recent experimental study in mice found that adiponectin, which is deficient in the obese, protects against the inflammatory effects of ozone exposure (31). Several studies have identified obesity as a risk factor for asthma (32,33).…”

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

“…Williams and colleagues showed that augmented airway inflammation and reactivity in obese mice in response to ozone depended on TNFa (22). Increased responses to subacute ozone exposure are also seen in adiponectin-deficient mice (adiponectin is decreased in obesity), and this appears to be related to signaling through IL-6 and IL-17A (76)(77)(78). The role of these mediators in increasing responses to ozone in obese individuals needs further exploration.…”