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Title: Regulation of IL-17A expression in mice following subacute ozone exposure.

Authors: Brand, Jeffrey D; Mathews, Joel A; Kasahara, David I; Wurmbrand, Alison P; Shore, Stephanie A

Published In J Immunotoxicol, (2016 May)

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.

PubMed ID: 27043160 Exiting the NIEHS site

MeSH Terms: Administration, Inhalation; Animals; Antigens, Differentiation/metabolism; Cells, Cultured; Dendritic Cells/immunology*; Gene Expression Regulation; Humans; Interleukin-1/metabolism; Interleukin-17/genetics; Interleukin-17/metabolism*; Interleukin-23/genetics; Interleukin-23/metabolism*; Interleukin-6/metabolism; Lung/immunology*; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Ozone/immunology*; Ozone/toxicity; fms-Like Tyrosine Kinase 3/genetics

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