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Title

Induction of CXCL1 by extracellular matrix and autocrine enhancement by interleukin-1 in rat pancreatic beta-cells

Authors
Ribaux, Pascale
Ehses, J. A.
Lin-Marq, Nathalie
Boni-Schnetzler, Marianne
Hammar, Eva
Donath, M. Y.
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Published in Endocrinology. 2007, vol. 148, no. 11, p. 5582-5590
Abstract 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.
Keywords AnimalsAutocrine Communication/ drug effectsCell Movement/drug effectsCells, CulturedChemokine CXCL1/ genetics/metabolism/pharmacology/secretionCulture Media, Conditioned/pharmacologyCytokines/geneticsExtracellular Matrix/ physiologyGene Expression Regulation/drug effectsGranulocytes/cytology/drug effectsInsulin-Secreting Cells/ drug effects/metabolism/secretionInterleukin-1/ pharmacologyMaleModels, BiologicalRatsRats, Wistar
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PMID: 17702850
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Other version: http://endo.endojournals.org/cgi/reprint/148/11/5582.pdf
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RIBAUX, Pascale et al. Induction of CXCL1 by extracellular matrix and autocrine enhancement by interleukin-1 in rat pancreatic beta-cells. In: Endocrinology, 2007, vol. 148, n° 11, p. 5582-5590. https://archive-ouverte.unige.ch/unige:8994

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Deposited on : 2010-07-12

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