Two different IL-13 receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway
Two different IL-13 receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway
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DOI：
10.1093/intimm/10.8.1103
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发表时间：
1998-08-01
影响因子：
4.4
通讯作者：
Puri, RK
中科院分区：
文献类型：
--
作者：
Murata, T;Husain, SR;Puri, RK
IL-13和IL-4是多效性免疫调节细胞因子，已显示在人成纤维细胞系中介导类似的显著作用，然而，其冗余作用的分子机制尚不清楚。在这里，我们研究了IL-13受体（IL-13R）的结构和通过IL-13和IL-4受体在非转化的正常皮肤成纤维细胞系中的信号转导的分子机制。我们证明，高亲和力IL-13 R在正常皮肤成纤维细胞系中表达。在[I-125] IL-13交联后，在sk559和sk574成纤维细胞系中观察到类似于60 - 70 kDa的条带。通过RT-PCR分析，表达IL-13 R α、IL-13 R α '和IL-4 R β链的mRNA;然而，显示参与和调节IL-4和IL-13结合的IL-2R γ链在所检测的任何细胞系中均不表达。Janus激酶（JAK）2和Tyk 2在sk559和sk574细胞系中响应IL-4或IL-13而磷酸化，JAK1也在两种细胞系中的一种中被磷酸化，而JAK3存在，但在所研究的任何细胞系中均不被磷酸化。信号转导和转录激活因子（STAT）6也响应于两种IL而被激活。胰岛素受体底物（IRS）-1被组成性磷酸化，并且其磷酸化水平响应于两种IL而增加。这些结果表明，在人成纤维细胞系中通过IL-13和IL-4受体的信号转导机制是相似的，并且这可能至少部分地负责这两种细胞因子的冗余效应。JAK2酪氨酸激酶而不是JAK3似乎在人成纤维细胞中IL-4和IL-13诱导的信号转导中起主要作用。
IL-13 and IL-4, pleiotropic immune regulatory cytokines, have been shown to mediate similar prominent effects in human fibroblast cell lines, However, molecular mechanisms for their redundant effects are not known. Here, we have investigated the structure of IL-13 receptors (IL-13R) and molecular mechanisms of signal transduction through IL-13 and IL-4 receptors in non-transformed normal skin fibroblast cell lines. We demonstrate that high-affinity IL-13R is expressed in normal skin fibroblast cell lines. Upon [I-125]IL-13 cross-linking, a similar to 60-70 kDa band was observed in sk559 and sk574 fibroblast cell lines. By RT-PCR analysis, mRNA for IL-13R alpha, IL-13R alpha' and IL-4R beta chains were expressed; however, the lL-2R gamma chain, shown to participate and modulate IL-4 and IL-13 binding, was not expressed in any of the cell lines examined, The Janus kinase (JAK)2 and Tyk2 were phosphorylated in response to IL-4 or IL-13 in sk559 and sk574 cell lines, JAK1 was also phosphorylated in one of two cell lines while JAK3 was present but not phosphorylated in any of the cell lines studied, A signal transduction and activator of transcription (STAT)6 was also activated in response to both IL. An insulin receptor substrate (IRS)-1 was constitutively phosphorylated and its phosphorylation level was augmented in response to both IL, These results suggest that the mechanism of signal transduction through IL-13 and IL-4 receptors in human fibroblast cell lines is similar, and this may, at least in part, be responsible for the redundant effects of these two cytokines, In addition, JAK2 tyrosine kinase instead of JAK3 appears to play a major role in IL-4- and IL-13-induced signal transduction in human fibroblasts.