Inhibition of transforming growth factor-β signalling attenuates interleukin (IL)-18 plus IL-2-induced interstitial lung disease in mice

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  • S Segawa
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • D Goto
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • Y Yoshiga
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • M Sugihara
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • T Hayashi
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • Y Chino
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • I Matsumoto
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • S Ito
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
  • T Sumida
    Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

書誌事項

公開日
2010-01-19
権利情報
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1111/j.1365-2249.2010.04094.x
公開者
Oxford University Press (OUP)

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説明

<jats:title>Summary</jats:title><jats:p>Interstitial lung disease (ILD) is an intractable disease induced by various factors in humans. However, there is no universally effective treatment for ILD. In this study, we investigated the role of transforming growth factor (TGF)-β signalling in the pathogenesis of ILD by using model mice. Injection of interleukin (IL)-18 plus IL-2 in C57BL6 (B6) mice resulted in acute ILD by infiltration of natural killer (NK) cells and a significant increase of TGF-β mRNA in the lung. To examine the pathogenetic role of TGF-β in ILD mice, we used SB-431542 (4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]-benzamide), which is a potent and selective inhibitor of TGF-β receptor I (TβRI), also known as activin receptor-like kinase 5 (ALK5). Treatment of B6-ILD mice with SB-431542 resulted in improvement of ILD, delay in mortality, reduction of the expression of interferon (IFN)-γ and IL-6 in the lungs. The same treatment also decreased significantly the percentage of natural killer (NK) cells in the lungs (P &lt; 0·05) and mRNA expression levels of certain chemokines such as CCL2, CCL3, CCL4, CCL5 and CXCL10 in B6-ILD. These findings were confirmed by IL-18 plus IL-2 treatment of Smad3-deficient (Smad3–/–) mice (P &lt; 0·05). Our results showed that inhibition of TGF-β signalling reduced the percentage of NK cells and the expression of certain chemokines in the lungs, resulting in improvement of ILD. The findings suggest that TGF-β signalling may play an important role in the pathogenesis of IL-18 plus IL-2-induced ILD in mice.</jats:p>

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