1. The Ph.D. Program of Biotechnology and Biomedical Industry, China Medical University, Taichung, Taiwan.
2. Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan
3. School of Medicine, China Medical University, Taichung, Taiwan
4. Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
5. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
6. Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
7. Department of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
8. Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
9. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
10. Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
11. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to inflammatory events in various diseases, although its role in RA pathology is uncertain. Analysis of the Gene Expression Omnibus GSE55235 dataset revealed high levels of expression of the adipokine nesfatin-1 in human RA synovial tissue. Similarly, our human synovial tissue samples exhibited increasing levels of nesfatin-1 expression and Ccl2 mRNA expression. Nesfatin-1-induced stimulation of CCL2 expression and monocyte migration involved the MEK/ERK, p38, and NF-κB signaling pathways. Notably, nesfatin-1-induced increases in CCL2 expression favored M1 macrophage polarization, which increased the expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Finally, nesfatin-1 shRNA ameliorated the severity of inflammatory disease and reduced levels of M1 macrophage expression in CIA mice. Our studies confirm that nesfatin-1 appears to be worth targeting in RA treatment.
Keywords: rheumatoid arthritis, nesfatin-1, CCL2, M1 macrophages, synovial fibroblasts