CXCL13 promotes TNF- α synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation

Biochem Pharmacol. 2024 Feb 1;221:116037. doi: 10.1016/j.bcp.2024.116037. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a well-known autoimmune disorder associated with joint pain, joint swelling, cartilage and bone degradation as well as deformity. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a crucial role in multiple cellular pathogenesis processes, including RA. TNF-α is a vital proinflammatory factor in the progression of RA. However, the role of CXCL13 in TNF-α production in RA has not been fully explored. Our analysis of both database and clinical samples revealed higher levels of CXCL13 and TNF-α in RA samples compared to healthy controls. CXCL13 concentration-dependently induces TNF-α synthesis in RA synovial fibroblasts. CXCL13 enhances TNF-α expression by interacting with the CXCR5 receptor, activating the ERK/p38 pathways, and inhibiting miR-330-3p generation. Importantly, treatment with CXCL13 shRNA counteracted the upregulation of TNF-α production induced by collagen-induced arthritis. Our findings support the notion that CXCL13 is a promising target in the treatment of RA.PMID:38301965 | DOI:10.1016/j.bcp.2024.116037
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research