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Moxibustion inhibits the macrophage M1 polarization toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway by regulating T-cell immunoglobulin and mucin-containing protein-3 in rheumatoid arthritis
Received date: 2023-09-11
Accepted date: 2023-12-05
Online published: 2024-11-12
Supported by
National Natural Science Foundation of China: Study on Immunoregulatory Mechanism of Moxibustion "Regulating Weiqi" to Regulate the Intrasynovial Environment Steady State in Rheumatoid Arthritis Model Rats based on the Skin-resident Memory T cells- Growth Arrest-specific 6/ Mer Tyrosine Kinase(82374587);National Natural Science Foundation of China: Study on the Immune Mechanisms of Macrophage M1/M2 Polarization in the Treatment of Rheumatoid Arthritis by Moxibustion "Strengthening Body Resistance and Eliminating Evil"(81973959);National Key R&D Program of China: Research on the Functional Characteristics of "Special Effects" and "Common Effects" of Acupoints(2019YFC1709001);Science and Technology Innovation Seedling Project of Sichuan Province: based on Macrophage M1 Polarization Signaling Pathway Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor kappa B and its Regulatory Molecule T-cell Immunoglobulin and Mucin-containing Protein-3 Exploring the Effect Mechanism of Moxibustion on Experimental Rheumatoid Arthritis Model(2022037)
OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis (RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3 (TIM-3) and subsequently modulating the macrophage M1 polarization toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) signaling pathway.
METHODS: We utilized moxibustion treatment in RA rat models using the Zusanli (ST36) and Shenshu (BL23) acupoints. Hematoxylin and eosin (HE) staining was used to observe the pathological changes of the synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Enzyme-linked immunosorbent assay (ELISA) was applied to verify the efficacy of moxibustion in reducing inflammation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of the TIM-3/TLR4-MyD88-NF-κB signaling pathway-related molecules, and Western blot was used to detect the contents of synovial NF-κB.
RESULTS: We established the Freund's complete adjuvant (FCA)-induced RA model in rats. The expression level of M1 polarization signaling pathway TLR4-MyD88-NF-κB and the inflammatory factors interleukin-12(IL-12), tumor necrosis factor alpha (TNF-α), and tumor necrosis factor beta (TNF-β) were significantly increased in the RA model. After moxibustion treatment, the expression level of TLR4-MyD88-NF-κB was significantly decreased, and the inflammatory factors IL-12, TNF-α, and TNF-β were decreased, but the expression level was significantly increased in the RA model. When TIM-3 expression was inhibited, the expression level of TLR4-MyD88-NF-κB, and the inflammatory factors IL-12, TNF-α, and TNF-β were not suppressed, even after moxibustion treatment.
CONCLUSIONS: Moxibustion regulates the key target TIM-3 by acting on the Zusanli (ST36) and Shenshu (BL23) points, thereby inhibiting the M1 polarization of macrophages; that is, it inhibits the TLR4-MyD88-NF-κB signaling pathway, and finally achieves alleviation of pathological changes and anti-inflammatory effects.
Kun LUO , Yumei ZHONG , Yanding GUO , Linlin ZHANG , Danhui HU , Wenbin MA , Xin YANG , Haiyan ZHOU . Moxibustion inhibits the macrophage M1 polarization toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway by regulating T-cell immunoglobulin and mucin-containing protein-3 in rheumatoid arthritis[J]. Journal of Traditional Chinese Medicine, 2024 , 44(6) : 1227 -1235 . DOI: 10.19852/j.cnki.jtcm.2024.06.009
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