Synergistic Activations of REG Iα and REG Iβ Promoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human Pancreatic β Cells

Figure 1

Effects of cytokines, β-cell toxic agents, and growth factors on the transcription of (a) REG Iα, (b) REG Iβ, (c) REG III, (d) HIP/PAP, and (e) REG IV in human 1.1B4 β cells. Cells were transfected with the human REG family gene reporter plasmids and treated as follows: 1, No addition; 2, Dx (100 nM); 3, IL-6 (20 ng/mL); 4, IL-6 + Dx; 5, IL-1β (300 U/mL); 6, IL-1β + Dx; 7, TNF-α (370 U/mL); 8, TNF-α + Dx; 9, IFN-γ (100 U/mL); 10, IFN-γ + Dx; 11, IL-1β (60 U/mL) + TNF-α (185 U/mL) + IFN-γ (14 U/mL); 12, IL-1β + TNF-α + IFN-γ + Dx; 13, IL-22 (10 ng/mL); 14, IL-22 + Dx; 15, IL-22 + IL-6 + Dx; 16, IFN-β (1500 U/mL); 17, IFN-β + Dx; 18, IL-8 (100 nM); 19, IL-8 + Dx; 20, PDGF (1 U/mL); 21, PDGF + Dx; 22, amino acids (5 times greater than that in RPMI 1640 medium); 23, palmitate (100 μM); 24, H₂O₂ (10 μM); 25, SNAP (250 μM); 26, STZ (2 mM); 27, STZ + Dx. The promoter activity was normalized for variations in transfection efficiency using β-galactosidase activity as an internal standard. Fold increase is calculated by dividing the promoter activity of stimulated cells by that of unstimulated cells (column 1). The broken line corresponds to 4-fold increase. Data are expressed as means ± SE for each group ((a) -4, (b–e) ). Transcriptional activities of no. 4 and 15 (IL-6 + Dx and IL-22 + IL-6 + Dx) in panels (a), (b), and (d) were significantly () and prominently (over 4 fold) increased.

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