RRC ID 42684
著者 Nakagome K, Dohi M, Okunishi K, Tanaka R, Miyazaki J, Yamamoto K.
タイトル In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-beta in the lung.
ジャーナル Thorax
Abstract BACKGROUND:Idiopathic pulmonary fibrosis is a devastating disorder for which there is no effective treatment. Transforming growth factor (TGF)-beta 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-beta 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-beta 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-beta1 in the lung. Immunohistochemical analyses showed that alveolar macrophages were one of the major sources of TGF-beta1 and IL-10 diminished the intensity of the staining. IL-10 also suppressed the expression of alphaV beta6 integrin, a molecule that plays an important role in TGF-beta activation, on lung epithelial cells. Alveolar macrophages from bleomycin injected mice produced TGF-beta1 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-beta in the lung and thus attenuates pulmonary fibrosis, even when delivered in the chronic phase.
巻・号 61(10)
ページ 886-94
公開日 2006-10-1
DOI 10.1136/thx.2005.056317
PII thx.2005.056317
PMID 16809410
PMC PMC2104751
MeSH Animals Bleomycin / toxicity* Bronchoalveolar Lavage Fluid / chemistry Bronchoalveolar Lavage Fluid / cytology Cell Line Gene Transfer Techniques Genetic Therapy / methods Immunohistochemistry Integrin alpha6 / pharmacology Interleukin-10 / administration & dosage* Interleukin-10 / genetics Macrophages, Alveolar / metabolism Male Mice Mice, Inbred C57BL Plasmids Pulmonary Fibrosis / therapy* Transforming Growth Factor beta / antagonists & inhibitors*
IF 10.844
引用数 93
WOS 分野 RESPIRATORY SYSTEM
リソース情報
ヒト・動物細胞 J774.1(RCB0434)