Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs
Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs
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DOI：
10.1152/ajplung.00170.2004
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发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Lungarella, G
中科院分区：
文献类型：
--
作者：
Cavarra, E;Carraro, F;Lungarella, G
对博莱霉素的纤维化诱导作用的敏感性因种属而异，其原因尚不清楚。不同品系小鼠中反应的变异性已得到充分证明。最近的证据表明，上调表达的细胞因子和细胞因子受体可能参与。我们评估了一些细胞因子及其受体在C57 Bl/6 J博莱霉素敏感和Balb/C博莱霉素耐药小鼠中的表达模式。在乙醚麻醉下，两种品系的动物经气管内接受盐水（50穆尔）或博来霉素（0.1 U/50穆尔）。在处理后的不同时间，通过组织化学分析肺的细胞因子和细胞因子受体，并通过RNA酶保护测定分析其mRNA。在两种菌株中均观察到TNF-α和IL-1 β的表达显著增加。然而，仅在C57 B1/6 J敏感动物中观察到TNF-α和IL-1受体的肺表达上调。从63 h开始，该特征明显。除了TNF-α，博来霉素给药还导致8小时时两种品系的肺中TGF-β的表达上调，并且仅在C57 Bl/6 J小鼠中TGF-β受体I和II的表达增强。TGF-β受体表达上调之前，在该菌株中IL-4，IL-13和IL-13受体-α的表达增加（博来霉素后8小时），然后是gp 130和IL-6的上调。我们在细胞因子受体谱中观察到的差异可能为两种小鼠品系对博来霉素的不同纤维化反应提供了额外的解释。
The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 mul) or bleomycin (0.1 U/50 mul) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-alpha and IL-1beta was observed in both strains. However, an upregulated lung expression for TNF-alpha and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-alpha, bleomycin administration also resulted in the upregulated expression of TGF-beta in the lungs of both strains at 8 h and in an enhanced expression of TGF-beta receptors I and II in C57Bl/6J mice only. The upregulation of TGF-beta receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-alpha (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin.