B lymphocytes are critical for lung fibrosis control and prostaglandin E2 regulation in IL-9 transgenic mice.
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.
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
Simoen
Vincent
V
Barbarin
Virginie
V
Misson
Pierre
P
van den Brûle
Sybille
S
Delos
Monique
M
Knoops
Laurent
L
Renauld
Jean-Christophe
JC
Lison
Dominique
D
Huaux
François
F
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000071876:Prostaglandin-E Synthases; D011658:Pulmonary Fibrosis / Q000276:immunology*; D012822:Silicon Dioxide / Q000494:pharmacology; D013347:Subcellular Fractions
D016906:Interleukin-9; D012822:Silicon Dioxide; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone