B lymphocytes are critical for lung fibrosis control and prostaglandin E2 regulation in IL-9 transgenic mice

Am J Respir Cell Mol Biol. 2006 May;34(5):573-80. doi: 10.1165/rcmb.2004-0383OC. Epub 2006 Jan 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Collagen / metabolism
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / biosynthesis
  • Dinoprostone / metabolism*
  • Female
  • Gene Expression Regulation*
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology
  • Interleukin-9 / metabolism*
  • Intramolecular Oxidoreductases / metabolism
  • Lung / cytology
  • Lung / drug effects
  • Lung / pathology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Transgenic
  • Prostaglandin-E Synthases
  • Pulmonary Fibrosis / immunology*
  • Silicon Dioxide / pharmacology
  • Subcellular Fractions


  • Interleukin-9
  • Silicon Dioxide
  • Collagen
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Dinoprostone