Lung fibrosis induced by silica particles in NMRI mice is associated with an upregulation of the p40 subunit of interleukin-12 and Th-2 manifestations
Lung fibrosis induced by silica particles in NMRI mice is associated with an upregulation of the p40 subunit of interleukin-12 and Th-2 manifestations
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DOI：
10.1165/ajrcmb.20.4.3342
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发表时间：
1999-04-01
影响因子：
6.4
通讯作者：
Lison, D
中科院分区：
文献类型：
--
作者：
Huaux, F;Lardot, C;Lison, D
白细胞介素（IL）-12是主要由活化的巨噬细胞产生的细胞因子，其参与控制免疫应答的辅助性T细胞1/辅助性T细胞2（Th 1/Th 2）极化。为了检测其在肺纤维化发展中的潜在作用，我们检测了IL-12（p70）及其亚基的（蛋白质，信使RNA [mRNA]）肺匀浆、支气管肺泡灌洗液（BALF）中的p40和p35，和支气管肺泡灌洗（BAL）细胞培养在小鼠模型的解决性肺泡炎（RA）和纤维化肺泡炎（FA）的无机颗粒诱导（分别为二氧化锰[MnO 2]和结晶二氧化硅）。给予碳化钨（WC）作为阴性对照条件，碳化钨（WC）对肺部无害。FA特异性地伴随Th 2样极化，其特征在于BALF中高水平的免疫球蛋白（IG）G（1）和p40蛋白和mRNA的长期过度产生，但不是生物活性形式的IL-12（p70）。在RA模型中，p40应答仅是短暂的，并且Th 1样应答通过BALF中干扰素（IFN）-γ水平的增加和IgG（2a）的主导水平反映。综上所述，这些发现表明IL-12的p40亚基的产生和Th 2极化在吸入无机颗粒的肺部炎症和纤维化反应中起重要作用。
Interleukin (IL)-12 is a cytokine produced principally by activated macrophages which is involved in control of the T-helper 1/T-helper 2 cell (Th1/Th2) polarization of immune responses. To examine its potential involvement in the development of lung fibrosis, we examined the expression (protein, messenger RNA [mRNA]) of IL-12 (p70) and of its subunits (p40 and p35) in lung homogenates, bronchoalveolar lavage fluid (BALF), and bronchoalveolar lavage (BAL) cell cultures in mouse models of resolutive alveolitis (RA) and fibrosing alveolitis (FA) induced by inorganic particles (manganese dioxide [MnO2] and crystalline silica, respectively). The administration of tungsten carbide (WC), which behaved as an innocuous dust for the lung, served as a negative control condition. The FA was specifically accompanied by a Th2-like polarization characterized by high levels of immunoglobulin (Ig)G(1) in BALF and by a protracted overproduction of both p40 protein and mRNA, but not by the biologically active form of IL-12 (p70). In the RA model, the p40 response was only transient, and a Th1-like response was reflected by increased levels of interferon (IFN)-gamma and dominant levels of IgG(2a) in BALF. Taken together, these findings suggest that production of the p40 subunit of IL-12 and Th2 polarization play important roles in lung inflammatory and fibrotic responses to inhaled inorganic particles.