BACKGROUND: Interactions between chemokines @entity371 , @entity2842 , and @entity5737 and their receptors may mediate graft rejection following islet transplantation. The mechanisms regulating chemokine gene expression in pancreatic islet cells have not been well characterized. We examined the cytokine-induced gene expression profiles for several chemokines in a transformed pancreatic beta-cell line (MIN6) cotreated with an inhibitor of @entity842 synthase and in a mutated clone of MIN6 made to overexpress a dominant negative inhibitor of @entity2451 (IkappaBalphaM). METHODS: MIN6 and MIN6-IkappaBalphaM (Bm) cells were cultured in mixtures of @entity1356 and @entity310 or @entity1356 , @entity310 , and @entity379 plus/minus the @entity3623 inhibitor @entity7293 . RT-PCR and RNase Protection Assay were used to measure mRNA expression for the following chemokines: @entity371 , @entity10557 , @entity12868 , @entity2842 , and @entity5737 . Enzyme linked immunosorbant assay was used to measure @entity371 and @entity2842 protein release. RESULTS: Cytokine-treated MIN6 and Bm demonstrated increased expression of genes for @entity371 and @entity2842 . Expression in MIN6 was first detected at 2 h of incubation and peaked at 6 h. MIN6 demonstrated a more marked increase in chemokine gene expression for both @entity371 and @entity2842 and a more marked increase in @entity371 protein release than did Bm. There was no detectable gene expression for @entity10557 , @entity12868 , or @entity5737 from MIN6 or Bm. @entity7293 completely blocked NO production from MIN6 and Bm but had no effect on chemokine gene expression in either MIN6 or Bm. CONCLUSIONS: These results suggest that beta cells produce a complement of rejection-relevant chemokines in response to a proinflammatory stimulus and that pathways governing cytokine-induced chemokine gene expression in MIN6 are dependent on @entity2451 but independent of NO.

Proinflammatory cytokines induce XXXX -dependent/NO-independent chemokine gene expression in MIN6 beta cells.

@entity5737 :: ('6352', 'Gene') :: ['RANTES'] @entity2451 :: ('4790', 'Gene') :: ['NF-kappaB'] @entity1356 :: ('3553', 'Gene') :: ['IL-1beta'] @entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity12868 :: ('6351', 'Gene') :: ['MIP-1beta'] @entity2842 :: ('6347', 'Gene') :: ['MCP-1'] @entity7293 :: ('CHEBI:28229', 'Chemical') :: ['L-NMMA'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity379 :: ('3458', 'Gene') :: ['IFN-gamma'] @entity3623 :: ('4843', 'Gene') :: ['iNOS'] @entity371 :: ('3627', 'Gene') :: ['IP-10'] @entity10557 :: ('6348', 'Gene') :: ['MIP-1alpha']
@entity2451 :: (4790,Gene) :: ['NF-kappaB']
