Abstract
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 receptorfor 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-1 RI-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 O 3 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.
Original language | English (US) |
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Pages (from-to) | 477-484 |
Number of pages | 8 |
Journal | American journal of respiratory cell and molecular biology |
Volume | 37 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2007 |
Externally published | Yes |
Keywords
- Bronchoalveolar lavage
- Interleukin-6
- Macrophage
- Neutrophil
- Soluble tumor necrosis factor receptor
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology