Celastrol Regulates the Secretion of Interleukin-17 in Patients with Sympathetic Ophthalmia Through Signal Transducer and Activator of Transcription 3.

Abstract

Purpose: The excessive secretion of interleukin (IL)-17 contributes to the pathological process of sympathetic ophthalmia (SO). Celastrol is a naturally active product and exhibits an immunosuppressive effect. However, whether the supplementation of celastrol relieves SO remains unclear. Methods: The peripheral blood mononuclear cells (PBMCs) were extracted from the venous blood samples of 20 SO patients and 20 healthy controls, followed by stimulating with various concentrations of celastrol. The levels of IL-23 and IL-17 were measured by enzyme-linked immunosorbent assay and real-time polymerase chain reaction assay. The activation of the signal transducer and activator of transcription 3 (STAT3) in PBMCs of SO patients was detected by Western blot. Results: The levels of IL-23 and IL-17 in PBMCs isolated from SO patients were significantly increased compared with those in PBMCs isolated from healthy controls. Celastrol treatment inhibited the production of both IL-23 and IL-17 in PBMCs of SO patients in a dose-dependent manner. In PBMCs isolated from SO patients and healthy controls, the administration of recombinant human IL-23 (rIL-23) enhanced the production of IL-17, which was then suppressed by co-stimulation with celastrol. Also, celastrol treatment reduced rIL-23-induced phosphorylation of STAT3 in PBMCs isolated from SO patients. Conclusions: Celastrol can reduce the production of IL-17 in PBMCs of SO patients. The mechanism may be related to the reduction of IL-23 secretion, which in turn inhibits the phosphorylation of STAT3.