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Antcin K inhibits VCAM-1-dependent monocyte adhesion in human rheumatoid arthritis synovial fibroblasts

David AchudhanGraduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, TaiwanSunny Li‐Yun ChangGraduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, TaiwanShan‐Chi LiuDepartment of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, TaiwanYen‐You LinSchool of Medicine, China Medical University, Taichung, TaiwanWei‐Chien HuangGraduate Institute of Biomedical Science, College of Medicine, China Medical University, Taichung, TaiwanYang‐Chang WuChinese Medicine Research and Development Center, Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, TaiwanChien‐Chung HuangDivision of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, TaiwanChun‐Hao TsaiDepartment of Orthopedic Surgery, China Medical University Hospital, Taichung, TaiwanChih‐Yuan KoDepartment of Orthopedic Surgery, China Medical University Hospital, Taichung, TaiwanYueh‐Hsiung KuoChinese Medicine Research Center, China Medical University, Taichung, TaiwanChih‐Hsin TangChinese Medicine Research Center, China Medical University, Taichung, Taiwan
2022en
ABI

Аннотация

Background: (a medicinal mushroom endemic to Taiwan commonly used in Chinese medicine preparations), inhibits proinflammatory cytokine production and angiogenesis in human rheumatoid arthritis synovial fibroblasts (RASFs), major players in RA disease. Antcin K also inhibits disease activity in mice with collagen-induced arthritis (CIA). Up until now, the effects of Antcin K upon cell adhesion molecules (CAMs) were unknown. Methods: = 10 in each group) were retrieved from the Gene Expression Omnibus (GEO) database (accession code: GDS5401) to compare CAM and monocyte marker expressions. In addition, synovial tissue samples from six RA patients and six patients undergoing arthroscopy for trauma/joint derangement (healthy controls) were subjected to immunohistochemical (IHC) analysis. mRNA and protein expression levels were analyzed in RASFs using RT-qPCR (Reverse transcription-quantitative polymerase chain reaction) and Western blot. RASFs were incubated with Antcin K and examined for monocyte adherence by fluorescence microscopy. Ankle joint tissue specimens from a CIA mouse model and healthy controls were stained with hematoxylin and eosin (H&E) and Safranin-O/Fast Green to examine histological changes and evidence of bone loss. IHC analysis determined levels of vascular cell adhesion molecule 1 (VCAM-1) and CD11b in CIA ankle tissue and clinical synovial tissue. Results: Levels of VCAM-1 expression were higher in the GEO database specimens and the study's clinical samples of RA synovial tissue compared with the healthy specimens. Antcin K dose-dependently inhibited VCAM-1 expression and monocyte adhesion in RASFs. Antcin K also significantly inhibited levels of VCAM-1 and monocyte CD11b expression in CIA tissue. These effects appeared to be mediated by MEK1/2-ERK, p38, and AP-1 signaling. Conclusions: Antcin K seems promising for the treatment of RA and deserves further investigations.

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