Abstract

The inflammatory proliferation of fibroblast-like synoviocytes (FLSs) and functional imbalances in T lymphocytes play critical roles in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of Huayu Tongbi Fang (HYTB, a traditional herbal formula) in RA treatment has been validated. In this study, we aimed to explore the regulatory mechanisms of HYTB on the proliferation and differentiation of T lymphocytes, and the inhibitory effect of HYTB on inflammatory proliferation of FLSs. The RCS-364 (Rat FLSs) cells were cocultured with rat splenic lymphocytes that were induced by interleukin-1β in Transwell chambers. After freeze-dried HYTB powder treatment, the percentage of T-cell subset and apoptosis rates of FLSs were measured using flow cytometry. Furthermore, protein expression of key molecules of NF-κB and JAK/STAT signaling pathways was quantified using Western blot. The granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured using enzyme-linked immunosorbent assay. The results showed that HYTB could inhibit the inflammatory proliferation of FLSs through inducing cell apoptosis. Additionally, HYTB treatment could intervene in the proliferation and differentiation of T lymphocytes and regulate protein expression of key molecules in NF-κB and JAK/STAT cell signaling pathways. Moreover, it could inhibit FLS activation by suppressing GM-CSF production by T cells and FLSs. Therefore, the HYTB formula should be used as a traditional medicine against RA in modern complementary and alternative therapies.

Highlights

  • Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5%–1.0% of adults worldwide

  • Preparation of the Freeze-Dried Huayu Tongbi Fang (HYTB) Powder. e modified HYTB formula was composed of six medicinal herbs. e constitution ratio of the six herbs was composed of Ligusticum chuanxiong Hort [4], Dioscorea nipponica Makino [4], Radix Aconiti Lateralis Preparata [2], Astragalus membranaceus [4], Radix Paeoniae Alba [3], and Corydalis yanhusuo [3]. e herbal mixture was soaked in deionized water for 20 min and extracted with boiling water at 10 : 1 (v/ w) for 2.5 h. e extracted liquid was collected, and the herb residue was added with deionized water and boiled for another 1 h. e extracted liquid was collected and combined with the first one

  • HYTB Regulated the Differentiation of and Treg Cells of Lymphocytes in the Coculture System Induced by IL-1β

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Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5%–1.0% of adults worldwide. RA joint inflammation is associated with immune cell infiltration, synovial inflammatory hyperplasia, and excessive proinflammatory mediator production, eventually resulting in articular cartilage injury [1, 2]. The detailed etiology and pathogenesis of RA remain uncertain, recent studies have demonstrated that inflammatory proliferation and activation of fibroblast-like synoviocytes (FLSs) and abnormal T-cell subset differentiation play critical roles in RA pathogenesis [3, 4]. Abnormal balance of T helper cells, 1/. 2, and Treg/ 17 induces the inflammatory immune response and FLS activation. FLSs produce proinflammatory cytokines and chemokines, recruit effective T cells to synovial tissue in the joint, and initiate autoimmune arthritis

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