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Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13.

Authors: Williams, AS  Nath, P  Leung, SY  Khorasani, N  McKenzie, AN  Adcock, IM  Chung, KF 
Citation: Williams AS, etal., Eur Respir J. 2008 Sep;32(3):571-8. Epub 2008 Apr 16.
Pubmed: (View Article at PubMed) PMID:18417511
DOI: Full-text: DOI:10.1183/09031936.00121607

The present study aimed to determine whether the T-helper cell type 2-derived cytokines, interleukin (IL)-4 and -13, can modulate the lung response to ozone exposure. IL-13(-/-), IL-4/13(-/-) and IL-13-overexpressing transgenic (Tg) mice were exposed to ozone (3 ppm; 3 h) or air. Wild-type (Wt) Balb/c mice and transgenic-negative littermates (IL-13Wt) were used as controls for gene-deficient and IL-13Tg mice, respectively. IL-4/13(-/-) and IL-13(-/-) mice developed a lesser degree of ozone-induced airway hyperresponsiveness (AHR) while IL-13Tg mice developed a greater degree of AHR compared with ozone-exposed wild-type or IL-13Wt mice, respectively. Ozone caused a time-dependent increase of bronchoalveolar lavage (BAL) neutrophils and macrophages in wild-type mice, maximal at 20-24 h, which was attenuated in the IL-13(-/-) and IL-4/13(-/-) mice. In IL-13Tg mice, there was a greater increase in BAL neutrophils after ozone exposure compared with IL-13Wt mice. Using quantitative real-time PCR, ozone-induced mRNA expression for IL-6 and keratinocyte chemokine was further enhanced in IL-13(-/-) and IL-4/13(-/-) mice, and was inhibited in IL-13Tg mice. Macrophage inflammatory protein (MIP)-3alpha/CCL20 expression was enhanced after ozone exposure in wild-type mice, inhibited in IL-13(-/-) and IL-4/13(-/-) mice, while in IL-13Tg mice it was enhanced. A similar pattern of expression was observed with lipopolysaccharide-induced cytokine (LIX/CXCL5/ENA-78) expression. In conclusion, interleukin-13 augments ozone-induced airway hyperresponsiveness and neutrophilic inflammation, possibly through modulation of certain cytokines induced by ozone exposure.

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CRRD Object Information
CRRD ID: 5135242
Created: 2011-07-14
Species: All species
Last Modified: 2011-07-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.