RRC ID 78829
Author Chang JW, Liu SC, Lin YY, He XY, Wu YS, Su CM, Tsai CH, Chen HT, Fong YC, Hu SL, Huang CC, Tang CH.
Title Nesfatin-1 Stimulates CCL2-dependent Monocyte Migration And M1 Macrophage Polarization: Implications For Rheumatoid Arthritis Therapy.
Journal Int J Biol Sci
Abstract 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.
Volume 19(1)
Pages 281-293
Published 2023-1-1
DOI 10.7150/ijbs.77987
PII ijbsv19p0281
PMID 36594093
PMC PMC9760434
MeSH Adipokines / metabolism Animals Arthritis, Rheumatoid* / genetics Arthritis, Rheumatoid* / metabolism Chemokine CCL2 / metabolism Cytokines / metabolism Humans Macrophages / metabolism Mice Monocytes* / metabolism
Resource
Human and Animal Cells MH7A(RCB1512)