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

Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo
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DOI:
10.1152/ajplung.2000.278.5.l914
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发表时间:
2000-05-01
影响因子:
4.9
通讯作者:
Hayashi, S
Hayashi, S
中科院分区:
医学2区
文献类型:
--
作者:
Arai, T;Abe, K;Hayashi, S

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白细胞介素(IL)-10已被证明可以减少许多炎症反应。我们研究了IL-10在博莱霉素诱导的肺损伤模型中的体内作用。在第3天将日本血凝病毒(HVJ)-含人IL-10表达载体(hIL10-HVJ)的脂质体或作为对照的平衡盐溶液(con -HVJ)腹腔注射给小鼠。随后在第0天气管内滴注博来霉素(0.8 mg/kg)。hIL10-HVJ可显著抑制第7天支气管肺泡灌洗液髓过氧化物酶活性、第21天支气管肺泡灌洗液细胞肿瘤坏死因子α mRNA表达和全肺羟脯氨酸含量。然而,康特- hvj处理不能抑制这些参数。我们还研究了IL-10对人肺成纤维细胞系WI-38的体外作用。IL-10显著降低构成型和转化型生长因子刺激的I型胶原mRNA表达。而IL-10不影响血小板源性生长因子诱导的WI-38细胞增殖。这些数据表明外源性IL-10可能在肺纤维化的治疗中有用。
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-alpha 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-beta-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.