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J Immunol. 2012 May 1;188(9):4558-67. doi: 10.4049/jimmunol.1102363. Epub 2012 Apr 2.

Pulmonary inflammation induced by subacute ozone is augmented in adiponectin-deficient mice: role of IL-17A.

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  • 1Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.

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.

PMID:
22474022
[PubMed - indexed for MEDLINE]
PMCID:
PMC3345205
Free PMC Article

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