IL-9 protects against bleomycin-induced lung injury: involvement of prostaglandins.
IL-9 is a Th2 cytokine that exerts pleiotropic activities, and might be involved in the regulation of lung inflammatory processes. To characterize the activity of IL-9 on lung injury, we compared the pulmonary responses to bleomycin (blm) in IL-9 transgenic (Tg5) and wild-type (FVB) mice. Following intratracheal instillation of lethal doses of blm, the mortality rate was markedly reduced in Tg5 mice compared to their wild-type counterparts (ie, 25% mortality for Tg5 versus 85% for FVB mice, 21 days after instillation of 0.05U blm/mouse). Histological and biochemical analyses showed that blm induced less lung injury and less epithelial damage in Tg5 as compared to FVB animals. This protection of Tg5 mice was accompanied by an expansion of eosinophils and B cells in the lungs. In addition, TGF-beta and prostaglandin-E2 (PGE2) levels in broncho-alveolar lavage fluid were also increased in transgenic mice. The contribution of B cells and eosinophils to the protective mechanism did not appear essential since eosinophil-deficient (IL-5 KO) and B-deficient (muMT) mice overexpressing IL-9 were also resistant to high doses of blm. We could rule out that TGF-beta was a key factor in the protective effect of IL-9 by blocking this mediator with neutralizing antibodies. Indomethacin treatment, which inhibited PGE2 production in both strains, suppressed the protection in Tg5 mice, supporting the idea that IL-9 controls blm-induced lung injury through a prostaglandin-dependent mechanism.
Arras
Mohammed
M
Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, UCL, Clos Chapelle-aux-Champs, 30.54, 1200 Brussels, Belgium.
Louahed
Jamila
J
Heilier
Jean-François
JF
Delos
Monique
M
Brombacher
Frank
F
Renauld
Jean-Christophe
JC
Lison
Dominique
D
Huaux
François
F
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D016906:Interleukin-9 / Q000235:genetics / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D055370:Lung Injury; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011453:Prostaglandins / Q000502:physiology*; D013997:Time Factors; D014881:Water Supply
D016906:Interleukin-9; D011453:Prostaglandins; D001761:Bleomycin; D007770:L-Lactate Dehydrogenase; D007213:Indomethacin