Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo

Author:

Arai Toru1,Abe Kin'Ya2,Matsuoka Hiroto1,Yoshida Mitsuhiro3,Mori Masahide1,Goya Sho1,Kida Hiroshi1,Nishino Kazumi1,Osaki Tadashi1,Tachibana Isao1,Kaneda Yasufumi4,Hayashi Seiji1

Affiliation:

1. Department of Molecular Medicine and

2. Department of Pulmonary Disease, Higashiosaka City General Hospital, Higashiosaka 578-8588, Japan; and

3. Department of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039

4. Division of Gene Therapy Science, Osaka University Medical School, Suita, Osaka 565-0871;

Abstract

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day −3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-α mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-β-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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