Regulation of Th17 Cytokine-Induced Osteoclastogenesis via SKI306X in Rheumatoid Arthritis.

Hae-Rim Kim,Kyung-Ann Lee,Tae-Young Kim,Sang-Heon Lee,Kyoung-Woon Kim,Ji-Yeon Won,Hong-Ki Min,Bo-Mi Kim

doi:10.3390/jcm8071012

Abstract

This study aimed to investigate the regulatory effect of SKI306X, a mixed extract of three herbs, in T helper (Th)17 cytokine-induced inflammation and joint destruction in rheumatoid arthritis (RA). Synovial fibroblasts were isolated from RA patients and cultured with Th17 cytokines including interleukin (IL)-17, IL-21, and IL-22 and SKI306X, and tumor necrosis factor (TNF)-α, IL-1β, and receptor activator of nuclear factor kappa-Β ligand (RANKL) expression and production were investigated using real-time PCR and ELISA of culture media. After peripheral blood (PB) cluster of differentiation (CD)14+ monocytes were cultured in media supplemented with Th17 cytokines and SKI306X, tartrate-resistant acid phosphatase positive (TRAP+) multinucleated giant cells (mature osteoclasts) were enumerated and gene expression associated with osteoclast maturation was assessed via real-time PCR analysis. After PB monocytes were co-cultured with IL-17-stimulated RA synovial fibroblasts in the presence of SKI306X, osteoclast differentiation was assessed. When RA synovial fibroblasts were cultured with IL-17, IL-21, and IL-22, TNF-α, IL-1β, and RANKL expression and production were increased; however, SKI306X reduced cytokine expression and production. When PB monocytes were cultured in media supplemented with Th17 cytokines, osteoclast differentiation was stimulated; however, SKI306X decreased osteoclast differentiation and osteoclast maker expression. When PB monocytes were co-cultured with IL-17-stimulated RA synovial fibroblasts, osteoclast differentiation was increased; however, SKI306X decreased osteoclast differentiation and osteoclast maker expression. SKI306X reduced Th17 cytokine-induced TNF-α, IL-1β, and RANKL expression and osteoclast differentiation, providing novel insights into adjuvant therapy for regulating inflammation and joint destruction in RA.

Highlights

A few decades ago, Korean patients with rheumatoid arthritis (RA) received herbal medication and acupuncture before they visited rheumatologic clinics
When RA synovial fibroblasts were cultured in media supplemented with IL-17, IL-21, or IL-22, tumor necrosis factor (TNF)-α was upregulated; SKI306X reduced Th17 cytokine-induced TNF-α expression (Figure 1A), TNF-α production was increased upon IL-17 stimulation in culture media, and SKI306X reduced TNF-α production (Figure 1B)
When RA synovial fibroblasts were cultured in media supplemented with IL-17 or IL-22, IL-1β was upregulated; SKI306X reduced Th17 cytokine-induced IL-1β expression

Summary

Introduction

A few decades ago, Korean patients with rheumatoid arthritis (RA) received herbal medication and acupuncture before they visited rheumatologic clinics. They believed the herbal therapies could cure RA without any adverse effects. By the time these patients visited rheumatologists, they already had joint destruction and disability because of delayed treatment with disease-modifying antirheumatic drugs (DMARDs). Some patients prefer complementary and alternative medication, primarily including herbal medication [1,2]. According to the Korean RA registry (KORONA), 10.5% of patients received complementary and alternative medicines de novo and among them, 17% received herbal medication and 55% received acupuncture [3]

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