Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13.
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.
Williams
A S
AS
Experimental Studies, Airway Disease Section, National Heart & Lung Institute, Guy Scadding Building, Dovehouse St., London SW3 6LY, UK.
Nath
P
P
Leung
S-Y
SY
Khorasani
N
N
McKenzie
A N J
AN
Adcock
I M
IM
Chung
K F
KF
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology*; D054418:Chemokine CCL20 / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010126:Ozone / Q000009:adverse effects*
D054418:Chemokine CCL20; D018793:Interleukin-13; D015847:Interleukin-4; D010126:Ozone