Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by silica particles in a murine model
Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by silica particles in a murine model
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DOI：
10.1165/ajrcmb.24.4.4249
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发表时间：
2001-04-01
影响因子：
6.4
通讯作者：
Lison, D
中科院分区：
文献类型：
--
作者：
Arras, M;Huaux, F;Lison, D
我们研究了白介素9(IL-9)在结晶性二氧化硅颗粒诱导的肺纤维化中的作用。白介素9是一种激活B和T淋巴细胞的细胞因子，与哮喘有关。因此，我们比较了高表达IL-9的转基因小鼠(TG5)和它们的野生型小鼠(FVB)对二氧化硅(1和5毫克/动物，气管内)的反应。在二氧化硅治疗后2个月和4个月，组织学检查和测定肺组织羟脯氨酸含量显示，TG5小鼠的纤维化严重程度明显低于其野生型小鼠。C57BL/6小鼠腹腔注射IL-9也能降低二氧化硅诱导的肺纤维化的幅度。IL-9减轻肺纤维化与B淋巴细胞数量显著增加有关，无论是在支气管肺泡灌洗(BAL)中还是在肺实质中。在野生型动物中，二氧化硅诱导的纤维化与类T辅助细胞反应的标志物相关，如肺组织中IL-4水平上调和BAL中免疫球蛋白G1/lgG2a比率增加。免疫组织化学研究表明，与纤维化发展相关的IL-4上调主要定位于炎性肺泡巨噬细胞。在转基因小鼠中，二氧化硅处理对肺组织匀浆中的IL-4水平没有显著影响，并且观察到二氧化硅处理后lgG1/lgG2a比率降低。经二氧化硅处理后，两种菌株的干扰素-γ水平均显著降低。总之，这些观察结果表明，IL-9在肺纤维化中的抗纤维化作用与限制伴随肺纤维化的2型极化有关。
We examined the effect of interleukin (IL)-9, a cytokine active on B and T lymphocytes and associated with bronchial asthma, on the development of lung fibrosis induced by crystalline silica particles. Therefore, we compared the response to silica (1 and 5 mg/animal, intratracheally) in transgenic mice that constitutively express high levels of IL-9 (Tg5) and their wild-type counterparts (FVB). At 2 and 4 mo after treatment with silica, histologic: examination and measurement of lung hydroxyproline content showed that the severity of fibrosis was significantly less important in Tg5 mice than in their wild-type counterparts. Intraperitoneal injection of IL-9 in C57BL/6 mice also reduced the amplitude of silica-induced lung fibrosis. The reduction of lung fibrosis by IL-9 was associated with a significant expansion of the B-lymphocyte population, both in bronchoalveolar lavage (BAL) and in the pulmonary parenchyma. In wild-type animals, silica-induced fibrosis correlated with markers of a T helper 2-like response such as upregulation of IL-4 levels in lung tissue and an increased immunoglobulin tig) G1/lgG2a ratio in BAL. Immunohistochemical studies demonstrated that the upregulation of IL-4 associated with the development of fibrosis was mainly localized in inflammatory alveolar macrophages. In transgenic mice, the level of IL-4 in lung homogenates was not significantly affected by silica treatment, and a reduced lgG1/lgG2a ratio was observed upon treatment with silica. The levels of interferon-gamma were significantly decreased after silica treatment in both strains. Together, these observations point to an antifibrotic effect of IL-9 in pulmonary fibrosis associated with a limitation of the type 2 polarization which accompanies lung fibrosis.