en
Scientific article
English

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

Published inEndocrinology, vol. 148, no. 11, p. 5582-5590
Publication date2007
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
  • Animals
  • Autocrine Communication/ drug effects
  • Cell Movement/drug effects
  • Cells, Cultured
  • Chemokine CXCL1/ genetics/metabolism/pharmacology/secretion
  • Culture Media, Conditioned/pharmacology
  • Cytokines/genetics
  • Extracellular Matrix/ physiology
  • Gene Expression Regulation/drug effects
  • Granulocytes/cytology/drug effects
  • Insulin-Secreting Cells/ drug effects/metabolism/secretion
  • Interleukin-1/ pharmacology
  • Male
  • Models, Biological
  • Rats
  • Rats, Wistar
Citation (ISO format)
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. doi: 10.1210/en.2007-0325
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ISSN of the journal0013-7227
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