title: 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.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Luo
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Yin
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism*; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009536:Niacinamide / Q000502:physiology; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015533:Transcriptional Activation
chemical_list: D005938:Glucocorticoids; D015850:Interleukin-6; D051847:Lithostathine; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C497616:Reg1a protein, rat; C490253:Reg3b protein, mouse; D009536:Niacinamide; D003907:Dexamethasone; D008156:Luciferases