Synergistic activations of REG i α and REG i β promoters by IL-6 and glucocorticoids through JAK/STAT pathway in human pancreatic β cells

Reg (regenerating gene) gene was originally isolated from rat regenerating islets and its encoding protein was revealed as an autocrine/paracrine growth factor for β cells. rat reg gene is activated in inflammatory conditions for β cell regeneration. in human,although five functional reg family genes (reg iα,reg iβ,reg iii,hip/pap,and reg iv) were isolated,their expressions in β cells under inflammatory conditions remained unclear. in this study,we found that combined addition of il-6 and dexamethasone (dx) induced reg iα and reg iβ expression in human 1.1b4 β cells. promoter assay revealed that a signal transducer and activator of transcription- (stat-) binding site in each promoter of reg iα (tgccgggaa) and reg iβ (tgccaggaa) was essential for the il-6+dx-induced promoter activation. a janus kinase 2 (jak2) inhibitor significantly inhibited the il-6+dx-induced reg iα and reg iβ transcription. electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that il-6+dx stimulation increased stat3 binding to the reg iα promoter. furthermore,small interfering rna-mediated targeting of stat3 blocked the il-6+dx-induced expression of reg iα and reg iβ. these results indicate that the expression of reg iα and reg iβ should be upregulated in human β cells under inflammatory conditions through the jak/stat pathway. © 2015 akiyo yamauchi et al.