缺乏Gp-130的表达使胰腺β细胞系对IL-6家族细胞因子无反应

G. Naselli, H. Deaizpurua, H. Thomas, A. M. Johnston, T. Kay
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引用次数: 4

摘要

来自IL-6受体家族的细胞因子受体由配体特异性α链和一个共同的信号链gp-130组成,这也是高亲和力结合所必需的。从β-TC3 SV40 t抗原转化的胰岛素瘤细胞系中筛选了该受体家族成员,这些成员可能与β细胞发育和自身免疫相关。利用这些受体一致区域的简并寡核苷酸引物,鉴定了IL-11受体(α链)。尽管证实IL-11受体mRNA表达,但碘化生物活性IL-11不会特异性结合β-TC3细胞,gp-130依赖性细胞因子不会引发β细胞系的信号事件。这可以解释为在β细胞系和原代胰岛中缺乏gp-130蛋白或mRNA。我们从这些结果中得出结论,先前认识到的IL-6家族成员细胞因子对胰岛的影响必须通过胰岛内的其他非β细胞间接产生,而不是直接作用于β细胞本身。
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Lack of Expression of Gp-130 Makes Pancreatic Beta Cell Lines Unresponsive to the IL-6 Family of Cytokines
Cytokine receptors from the IL-6 receptor family are comprised of ligand specific α chains and a common signalling chain, gp-130, which is also required for high affinity binding. A cDNA library generated from the β-TC3 SV40 T-antigen transformed insulinoma cell line was screened for members of this receptor family potentially relevant to both beta cell development and autoimmunity. Degenerate oligonucleotide primers to a consensus region of these receptors were used and the IL-11 receptor (α chain was identified. Despite confirmation of IL-11 receptor mRNA expression, iodinated bioactive IL-11 did not bind specifically to β-TC3 cells and gp-130-dependent cytokines did not elicit signalling events in beta cell lines. This was explained by absence of gp-130 protein or mRNA in the beta cell lines tested and in primary islets. We conclude from these resuits that the previously recognised effects of IL-6 family member cytokines on pancreatic islets must be indirect via other non-beta cells within the islet, rather than due to direct effects on beta cells themselves.
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