Transcriptional activation of Reg2 and Reg3β genes by glucocorticoids and interleukin-6 in pancreatic acinar and islet cells

Abstract: Reg family proteins are expressed in the pancreas and involved in pancreatitis and islet β-cell growth. In order to explore transcriptional control, we transfected luciferase reporter genes driven by Reg promoters into acinar AR42J and islet MIN6 cells. Dexamethasone (DEX) significantly increased the promoter expression of Reg2 and Reg3β genes and the levels of endogenous Reg3β mRNA and protein in AR42J cells. DEX-induced promoter activation was inhibited by the inhibitor of poly(ADP-ribose) polymerase, nicotinamide. In MIN6 cells, DEX moderately stimulated the transcription of Reg3β but not Reg2 promoter. While IL-6 alone had no effect, coculture with DEX produced a remarkable synergism on Reg3β gene transcription, which was abolished by nicotinamide. Our results demonstrated a significant and direct stimulation of Reg2 and Reg3β genes by glucocorticoids, all three were activated in response to inflammation such as in pancreatitis. Prominent stimulation of specific Reg genes by glucocorticoids may constitute a functional synergism. [Copyright &y& Elsevier]