Type I Interleukin-1 Receptor Is Required for... : American Journal of Respiratory Cell and Molecular Biology (original) (raw)

Type I Interleukin-1 Receptor Is Required for Pulmonary Responses to Subacute Ozone Exposure in Mice

• Richard A. Johnston
• Joseph P. Mizgerd
• Lesley Flynt
• Lee J. Quinton
• Erin S. Williams
• Stephanie A. Shore

American Journal of Respiratory Cell and Molecular Biology

37

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4

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:p

477

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484

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October 2007

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| DOI: 10.1165/rcmb.2006-0315OC

Interleukin (IL)-1, a proinflammatory cytokine, is expressed in the lung after ozone (O3) exposure. IL-1 mediates its effects through the type I IL-1 receptor (IL-1RI), the only signaling receptor for both IL-1α and IL-1β. The purpose of this study was to determine the role of IL-1RI in pulmonary responses to O3. To that end, wild-type, C57BL/6 (IL-1RI+/+) mice and IL-1RI-deficient (IL-1RI−/−) mice were exposed to O3 either subacutely (0.3 ppm for 72 h) or acutely (2 ppm for 3 h). Subacute O3 exposure increased bronchoalveolar lavage fluid (BALF) protein, interferon-γ-inducible protein (IP)-10, soluble tumor necrosis factor receptor 1 (sTNFR1), and neutrophils in IL-1RI+/+ and IL-1RI−/− mice. With the exception of IP-10, all outcome indicators were reduced in IL-1RI−/− mice. Furthermore, subacute O3 exposure increased IL-6 mRNA expression in IL-1RI+/+, but not IL-1RI−/− mice. Acute (2 ppm) O3 exposure increased BALF protein, IL-6, eotaxin, KC, macrophage inflammatory protein (MIP)-2, IP-10, monocyte chemotactic protein-1, sTNFR1, neutrophils, and epithelial cells in IL-1RI+/+ and IL-1RI−/− mice. For IL-6, eotaxin, MIP-2, and sTNFR1, there were small but significant reductions of these outcome indicators in IL-1RI−/− versus IL-1RI+/+ mice at 6 hours after exposure, but not at other time points, whereas other outcome indicators were unaffected by IL-1RI deficiency. These results suggest that IL-1RI is required for O3-induced pulmonary inflammation during subacute O3 exposure, but plays a more minor role during acute O3 exposure. In addition, these results suggest that the induction of IL-6 via IL-1RI may be important in mediating the effects of O3 during subacute exposure.