Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking / 南方医科大学学报

<p><b>OBJECTIVE</b>Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.</p><p><b>METHOD</b>Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.</p><p><b>RESULT</b>Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.</p><p><b>CONCLUSION</b>Dhd can selectively suppress RORγt transcriptional activity.</p>

Expression of CD70 in T lymphocytes from patients with systemic lupus erythematosus / 中华皮肤科杂志

Objective To detect the expression of CD70 in peripheral T lymphocytes of patients with systemic lupus erythematosus (SLE) and the effect of azacitidine, an inhibitor of DNA methylation, on it. Methods Blood samples were obtained from 10 patients with active SLE (SLEDAI score ≥5), 10 patients with nonactive SLE (SLEDAI score < 5) and 10 normal human controls. Peripheral T lymphocytes were isolated and cultured for 72 hours. A part of the T lymphocytes from normal controls, which were cultured in the presence of azacitidine at 1 mol/L, served as the methylation-inhibited group. Semiquantitative reverse transcription PCR and flow cytometry were applied to detect the mRNA expression of CD70 and frequency of CD70+CD4+ cells in the cultured lymphocytes, respectively. Results The frequency of CD70+CD4+ lymphocytes was 14.55%±5.49% in normal control group, 85.25%±14.08% in active SLE group, 77.65% ±18.77% in nonactive SLE group, and 81.54%±8.71% in methylation-inhibited group. Compared with the normal control group, a significant increase was observed in both the frequency of CD70+CD4+ lymphocytes (all P < 0.01) and the expression of CD70 expression (all P < 0.05) in other three groups. There was a positive correlation between the frequency of peripheral CD70+CD4+ lymphocytes and disease activity of SLE in patients (r = 0.72, P < 0.05). Conclusions The elevated expression of CD70 appears to play a significant role in the immunologic disarrangement in SLE, and may act as a indicator of disease activity of this disease.