Development of a Topical Treatment for Psoriasis Targeting RORγ: From Bench to Skin
Fig 1
GSK2981278 is a strong RORγ-selective inverse agonist that inhibits activation of the il17 promoter.
(A) RORE-dependent activation was examined using a Luciferase-based reporter (pGL4-27-5xRORE) CHO Tet-on cell line. Percent inhibition was calculated relative to vehicle (DMSO). cAMP-based cell viability was measured. (B) Activation of the human il17 promoter in compound-treated Jurkat cells co-transfected with control or reporter plasmid. D, indicates DMSO. (C-D) Mammalian mono-hybrid (C) or two-hybrid (D) analysis was performed following co-transfection with control or reporter plasmids +/- compound. (E) pCMV10-3xFlag-RORγ-transfected Jurkat cells were stimulated for 24 hrs and il17 mRNA levels determined by qRT-PCR. (F) ChIP-qPCR was performed in pCMV10-3xFlag-RORγ-transfected Jurkat cells. All experiments were independently performed at least twice. Significant inhibition was determined by Student’s t test. (* p≤0.01).