title: Regulation of IL-17A expression in mice following subacute ozone exposure.
abstract: Exposure to subacute ozone (O3) causes pulmonary neutrophil recruitment. In mice, this recruitment requires IL-17A. Ozone also causes expression of IL-23 and IL-1, which can induce IL-17A. The purpose of this study was to examine the hypothesis that IL-23 and IL-1 contribute to IL-17A expression and subsequent neutrophil recruitment after subacute O3 exposure. Wild-type, IL-23(-/-), and Flt3l(-/-) mice were exposed to air or 0.3 ppm O3 for 72 h. Flt3l(-/-) mice lack conventional dendritic cells (cDC) that can express IL-23 and IL-1. Other wild-type mice were pre-treated with saline or the IL-1R1 antagonist anakinra prior to O3 exposure. After exposure, bronchoalveolar lavage (BAL) was performed and lung tissue harvested. The results indicated that pulmonary Il17a mRNA abundance and IL-17A(+) F4/80(+) cells were significantly reduced in O3-exposed IL-23(-/-) vs in wild-type mice. In contrast, anakinra had no effect on Il23a or Il17a pulmonary mRNA abundance or on BAL concentrations of the neutrophil survival factor G-CSF, but anakinra did reduce BAL neutrophil numbers, likely because anakinra also reduced BAL IL-6. Compared to air, O3 caused a significant increase in DC numbers in wild-type, but not in Flt3(-/-) mice. However, there was no significant difference in Il23a or Il17a mRNA abundance or in BAL neutrophil count in O3-exposed Flt3(-/-) vs in wild-type mice. From these results, it was concluded that IL-23 but not IL-1 contributes to the IL-17A expression induced by subacute O3 exposure. Induction of IL-23 by O3 does not appear to require cDC.
authors.affiliation: a Molecular and Integrative Physiological Sciences Program, Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Brand
authors.affiliation: a Molecular and Integrative Physiological Sciences Program, Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Mathews
authors.affiliation: a Molecular and Integrative Physiological Sciences Program, Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Kasahara
authors.affiliation: a Molecular and Integrative Physiological Sciences Program, Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Alison P
authors.initials: AP
authors.lastname: Wurmbrand
authors.affiliation: a Molecular and Integrative Physiological Sciences Program, Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Shore
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D010126:Ozone / Q000276:immunology* / Q000633:toxicity; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D007375:Interleukin-1; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; C036763:monocyte-macrophage differentiation antigen; D010126:Ozone; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3
keywords: IL-1; IL-23; IL-6; dendritic cells; neutrophils