As we showed previously, the extracellular matrix (ECM) derived from rat bladder carcinoma cells (804G-ECM) has positive effects on rat primary -cell function and survival in vitro. The aim of this study was to define -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 to poly-L-lysine: CXCL1, CXCL2, IP10 and IL-1. A time-course experiment indicated that maximal induction by 804G-ECM of CXCL1/2 and IP10 occurred at 4 hours. Stimulation of CXCL1 release by -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 1 integrins and laminin-5 (a major component of 804G-ECM) with specific antibodies resulted in a 40–50% inhibition of CXCL1 expression. Using the NF-B pathway inhibitor Bay 11–7082 it is demonstrated that CXCL1 expression and secretion are dependent on NF-B activation. IL-1 secreted by -cells plated on 804G-ECM was found to be a key soluble mediator, since 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.