Type I interleukin-1 receptor is required for pulmonary responses to subacute ozone exposure in mice.
Interleukin (IL)-1, a proinflammatory cytokine, is expressed in the lung after ozone (O(3)) exposure. IL-1 mediates its effects through the type I IL-1 receptor (IL-1RI), the only signaling receptor for both IL-1alpha and IL-1beta. The purpose of this study was to determine the role of IL-1RI in pulmonary responses to O(3.) To that end, wild-type, C57BL/6 (IL-1RI(+/+)) mice and IL-1RI-deficient (IL-1RI(-/-)) mice were exposed to O(3) either subacutely (0.3 ppm for 72 h) or acutely (2 ppm for 3 h). Subacute O(3) exposure increased bronchoalveolar lavage fluid (BALF) protein, interferon-gamma-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 O(3) exposure increased IL-6 mRNA expression in IL-1RI(+/+), but not IL-1RI(-/-) mice. Acute (2 ppm) O(3) 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 O(3)-induced pulmonary inflammation during subacute O(3) 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 O(3) during subacute exposure.
Johnston
Richard A
RA
Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. rajohnst@utmb.edu
Mizgerd
Joseph P
JP
Flynt
Lesley
L
Quinton
Lee J
LJ
Williams
Erin S
ES
Shore
Stephanie A
SA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects
D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; D018799:Intercellular Adhesion Molecule-1; D010126:Ozone