title: 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.
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Kasahara
authors.forename: Hye Y
authors.initials: HY
authors.lastname: Kim
authors.forename: Alison S
authors.initials: AS
authors.lastname: Williams
authors.forename: Norah G
authors.initials: NG
authors.lastname: Verbout
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tran
authors.forename: Huiqing
authors.initials: H
authors.lastname: Si
authors.forename: Allison P
authors.initials: AP
authors.lastname: Wurmbrand
authors.forename: Jordan
authors.initials: J
authors.lastname: Jastrab
authors.forename: Christopher
authors.initials: C
authors.lastname: Hug
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Shore
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010083:Oxidants, Photochemical / Q000009:adverse effects* / Q000494:pharmacology; D010126:Ozone / Q000009:adverse effects* / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D000943:Antigens, Differentiation; D016207:Cytokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D008070:Lipopolysaccharides; D010083:Oxidants, Photochemical; D016692:Receptors, Antigen, T-Cell, gamma-delta; D010126:Ozone