Induction of CXCL1 by Extracellular Matrix and Autocrine Enhancement by Interleukin-1 in Rat Pancreatic β-Cells

Autor: Pascale Ribaux, Jan A. Ehses, Fabio Carrozzino, Nathalie Lin-Marq, Jean-Claude Irminger, Marianne Böni-Schnetzler, Philippe A. Halban, Marc Y. Donath, Eva Hammar
Rok vydání: 2007
Předmět:
Male
medicine.medical_specialty
Chemokine CXCL1
medicine.medical_treatment
Integrin
Gene Expression Regulation/drug effects
Cell Movement/drug effects
Biology
Models
Biological
Culture Media
Conditioned/pharmacology
Chemokine CXCL1/ genetics/metabolism/pharmacology/secretion
Extracellular matrix
Endocrinology
Cell Movement
Insulin-Secreting Cells
Internal medicine
Gene expression
Autocrine Communication/ drug effects
medicine
Animals
Secretion
Interleukin-1/ pharmacology
Rats
Wistar
Autocrine signalling
Cells
Cultured
ddc:616
Extracellular Matrix/ physiology
Cytokines/genetics
Interleukin
Insulin-Secreting Cells/ drug effects/metabolism/secretion
Molecular biology
Extracellular Matrix
Rats
Autocrine Communication
CXCL2
Cytokine
Gene Expression Regulation
Granulocytes/cytology/drug effects
Culture Media
Conditioned
biology.protein
Cytokines
Granulocytes
Interleukin-1
Zdroj: Endocrinology, Vol. 148, No 11 (2007) pp. 5582-5590
ISSN: 1945-7170
0013-7227
DOI: 10.1210/en.2007-0325
Popis: 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.
Databáze: OpenAIRE
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