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INTERSTITIAL LUNG DISEASE |
1 Pulmonary Division, Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
2 Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan
Correspondence to:
Correspondence to:
Dr M Dohi
Pulmonary Division, Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;mdohi-tky{at}umin.ac.jp
Backgroud: Idiopathic pulmonary fibrosis is a devastating disorder for which there is no effective treatment. Transforming growth factor (TGF)-ß plays a critical role in provoking fibrosis. Interleukin (IL)-10 is a potent immunosuppressive cytokine but its effect on the fibrosing process is unclear. A study was undertaken to examine whether IL-10 affects the production and activation of TGF-ß and thus can attenuate the fibrosis.
Methods: Mice were given an intratracheal injection of bleomycin. On day 1 or 14, IL-10 gene was delivered by rapid intravenous injection of Ringer’s solution containing plasmid. Two weeks after the plasmid injection the mice were examined for fibrosis. The effect of IL-10 on TGF-ß production by alveolar macrophages was assessed.
Results: Even when delivered during the fibrosing phase, IL-10 gene significantly suppressed the pathological findings, hydroxyproline content, and production of both active and total forms of TGF-ß1 in the lung. Immunohistochemical analyses showed that alveolar macrophages were one of the major sources of TGF-ß1 and IL-10 diminished the intensity of the staining. IL-10 also suppressed the expression of 
Vß6 integrin, a molecule that plays an important role in TGF-ß activation, on lung epithelial cells. Alveolar macrophages from bleomycin injected mice produced TGF-ß1 spontaneously ex vivo, which was significantly suppressed by treatment of the mice in vivo or by treatment of the explanted macrophages ex vivo with IL-10.
Conclusion: IL-10 suppresses the production and activation of TGF-ß in the lung and thus attenuates pulmonary fibrosis, even when delivered in the chronic phase.
Abbreviations: BAL, bronchoalveolar lavage; hpf, high power fields; IL, interleukin; IPF, idiopathic pulmonary fibrosis; LPS, lipopolysaccharide; TGF, transforming growth factor
Keywords: interleukin 10; gene therapy; transforming growth factor ß; idiopathic pulmonary fibrosis
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