Published ahead of print on January 19, 2006, doi:10.1165/rcmb.2004-0383OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 5, May 2006, 573-580 A more recent version of this article appeared on May 1, 2006
Submitted on December 2, 2004 B-Lymphocytes are Critical for Lung Fibrosis Control and PGE2 Regulation in IL-9 Transgenic MiceMohammed Arras1,1 Unit of Industrial Toxicology and Occupational Medicine, Universite catholique de Louvain, Faculty of Medicine, Brussels, Belgium, 2 Unit of Experimental Medicine and Ludwig Institute for Cancer Research, Universite catholique de Louvain, Faculty of Medicine, Brussels, Belgium, 3 Laboratory of Pathology, Universite catholique de Louvain, University Hospital of Mont-Godinne, Yvoir, Belgium * To whom correspondence should be addressed. 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;24:368-75). 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 anti-fibrotic 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 anti-fibrotic mediator PGE2 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-deficient 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 COX2 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.
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