Triptolide alleviates the development of inflammation in ankylosing spondylitis via the NONHSAT227927.1/JAK2/STAT3 pathway.

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease that can destroy the affected joints. Triptolide (TPL), a key active ingredient of the traditional Chinese medicine Tripterygium wilfordii exhibits promising efficacy in rheumatic immune disease with its anti-inflammatory effects. The present study aimed to elucidate the mechanism of TPL in treatment of AS by regulating the long non-coding RNA (lncRNA) NONHSAT227927.1. The role and underlying mechanisms of TPL in the development of inflammation in AS were assessed. In vivo, the expression of NONHSAT227927.1 in AS was detected by reverse transcription-quantitative (RT-q)PCR. Correlation analysis and binary logistic regression were performed between immune and inflammatory indicators, perception scale scores of patients and NONHSAT227927.1. In vitro, Cell Counting Kit-8 was used to evaluate the activity of AS-fibroblast-like synoviocytes (FLSs) following TPL exposure. AS-FLS inflammation was assessed by qPCR and ELISA. The interaction between TPL and JAK2 and STAT3 was verified by molecular docking and the JAK2/STAT3 pathway components were detected by western blotting. NONHSAT227927.1 was knocked down by small interfering RNA to determine its role. NONHSAT227927.1 was highly expressed in vivo and positively correlated with disease duration, disease duration, Body mass index (BMI), C-reactive protein (CRP), Visual analog scale (VAS), Visual analog scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Metrology Index, among which ESR and VAS and BASDAI score were risk factors for NONHSAT227927.1. TPL downregulated pro-inflammatory factors in AS-FLSs and inhibited the JAK2/STAT3 pathway via NONHSAT227927.1. TPL inhibited inflammatory factors in AS-FLSs and alleviated inflammatory responses via the NONHSAT227927.1/JAK2/STAT3 axis.