Induction of CXCL1 by extracellular matrix and autocrine enhancement by interleukin-1 in rat pancreatic beta-cells.
Induction of CXCL1 by extracellular matrix and autocrine enhancement by interleukin-1 in rat pancreatic beta-cells.
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大鼠胰腺 β 细胞中细胞外基质诱导 CXCL1 和白细胞介素 1 增强自分泌。
DOI：
10.1210/en.2007-0325
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发表时间：
2007
期刊：
影响因子：
4.8
通讯作者：
P. Halban
中科院分区：
文献类型：
--
作者：
P. Ribaux;J. Ehses;N. Lin;F. Carrozzino;M. Böni;E. Hammar;J. Irminger;M. Donath;P. Halban
如我们先前所示，来自大鼠膀胱癌细胞（804 G-ECM）的细胞外基质（ECM）对大鼠原代β细胞功能和体外存活具有积极作用。本研究的目的是确定由ECM诱导的β细胞基因，特别关注细胞因子。通过寡核苷酸微阵列、RT-PCR和原位杂交进行差异基因表达分析，以鉴定由该基质诱导的细胞因子mRNA。与多聚赖氨酸相比，804 G-ECM上有四种细胞因子过表达：C-X-C基序配体1（CXCL 1）、CXCL 2、干扰素诱导蛋白-10和IL-1 β。时程实验表明，804 G-ECM对CXCL 1/2和干扰素诱导蛋白-10的最大诱导发生在4 h。在蛋白质水平证实了804 G-ECM上的β细胞对CXCL 1释放的刺激。此外，分泌的CXCL 1显示出通过吸引大鼠粒细胞而具有功能活性。用特异性抗体阻止β 1整联蛋白和层粘连蛋白-5（804 G-ECM的主要成分）的相互作用导致CXCL 1表达的40-50%抑制。使用核因子-kappaB通路抑制剂Bay 11-7082，证明了CXCL 1的表达和分泌依赖于核因子-kappaB活化。发现由接种在804 G-ECM上的β细胞分泌的IL-1是关键的可溶性介质，因为用IL-1受体拮抗剂处理细胞显著降低了CXCL 1基因表达和分泌。可以得出结论，ECM诱导细胞因子的表达，包括CXCL 1与IL-1的放大作用，通过一个积极的自分泌反馈回路。
As we showed previously, the extracellular matrix (ECM) derived from rat bladder carcinoma cells (804G-ECM) has positive effects on rat primary beta-cell function and survival in vitro. The aim of this study was to define beta-cell genes induced by this ECM with a specific focus on cytokines. Analysis of differential gene expression by oligonucleotide microarrays, RT-PCR, and in situ hybridization was performed to identify cytokine mRNA induced by this matrix. Four cytokines were overexpressed on 804G-ECM compared with poly-L-lysine: C-X-C motif ligand 1 (CXCL1), CXCL2, interferon-inducible protein-10, and IL-1beta. A time-course experiment indicated that maximal induction by 804G-ECM of CXCL1/2 and interferon-inducible protein-10 occurred at 4 h. Stimulation of CXCL1 release by beta-cells on 804G-ECM was confirmed at the protein level. Moreover, secreted CXCL1 was shown to be functionally active by attracting rat granulocytes. Preventing the interaction of beta1 integrins and laminin-5 (a major component of 804G-ECM) with specific antibodies resulted in a 40-50% inhibition of CXCL1 expression. Using the nuclear factor-kappaB pathway inhibitor Bay 11-7082 it is demonstrated that CXCL1 expression and secretion are dependent on nuclear factor-kappaB activation. IL-1 secreted by beta-cells plated on 804G-ECM was found to be a key soluble mediator because treatment of cells with the IL-1 receptor antagonist significantly reduced both CXCL1 gene expression and secretion. It is concluded that ECM induces expression of cytokines including CXCL1 with amplification by IL-1 acting via a positive autocrine feedback loop.
DOI：
10.1530/acta.0.1130551
发表时间：
1986-12
期刊：
Acta endocrinologica
影响因子：
--
作者：
G. A. Spinas;T. Mandrup-Poulsen;J. Mølvig;Leif Bæk;Klaus Bendtzen;C. Dinarello;J. Nerup
通讯作者：
G. A. Spinas;T. Mandrup-Poulsen;J. Mølvig;Leif Bæk;Klaus Bendtzen;C. Dinarello;J. Nerup