Published ahead of print on January 19, 2006, doi:10.1165/rcmb.2004-0383OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2004-0383OC B Lymphocytes Are Critical for Lung Fibrosis Control and Prostaglandin E2 Regulation in IL-9 Transgenic MiceUnit of Industrial Toxicology and Occupational Medicine, Unit of Experimental Medicine and Ludwig Institute for Cancer Research, Faculty of Medicine, and Laboratory of Pathology, University Hospital of Mont-Godinne, Yvoir, Université catholique de Louvain, Brussels, Belgium Correspondence and requests for reprints should be addressed to François Huaux, Ph.D., Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, UCL, Clos Chapelle-aux-Champs, 30.54, 1200 Brussels, Belgium. E-mail: huaux{at}toxi.ucl.ac.be We previously showed that overexpression of IL-9 controls lung fibrosis induced by silica particles in mice (Arras and colleagues; Am J Respir Cell Mol Biol 2001;24:368–375). This protection was associated with an expansion of lung B lymphocytes. To explore the contribution of these cells in the protective effect of IL-9, we crossed IL-9 transgenic (IL-9+) and B-deficient (B–) mice. The antifibrotic effect of IL-9 was abolished in mice deficient in B lymphocytes (B–IL-9+) and restored by reconstituting these mice with B lymphocytes. The expression of the antifibrotic mediator prostaglandin (PG)E2 was markedly increased in the lung of IL-9+ mice at baseline, and similarly high levels were found in both wild-type and transgenic strains upon silica treatment. This PGE2 expression was completely abolished in B– mice, both at baseline and upon silica administration. In vitro, alveolar and peritoneal macrophages from IL-9+ mice had an increased capacity to produce PGE2 in response to LPS or silica. This capacity was markedly reduced in macrophages obtained from B– mice and restored by co-incubating macrophages with B lymphocytes from IL-9+ mice. The increased PGE2 response of IL-9+ macrophages was dependent on cyclooxygenase 2 expression, based on transcript analysis and inhibition by NS398. We conclude that B lymphocytes are essential for the protection against lung fibrosis and macrophage overexpression of PGE2 in IL-9 transgenic animals.
Key Words: B lymphocytes • cytokines • lipid mediators • lung • monocytes/macrophages This article has been cited by other articles:
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