RRC ID |
79279
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Author |
Achudhan D, Lai YL, Lin YY, Huang YL, Tsai CH, Ho TL, Ko CY, Fong YC, Huang CC, Tang CH.
|
Title |
CXCL13 promotes TNF-α synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation.
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Journal |
Biochem Pharmacol
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Abstract |
Rheumatoid 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.
|
Volume |
221
|
Pages |
116037
|
Published |
2024-3-1
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DOI |
10.1016/j.bcp.2024.116037
|
PII |
S0006-2952(24)00020-0
|
PMID |
38301965
|
MeSH |
Animals
Arthritis, Experimental*
Arthritis, Rheumatoid* / genetics
Autoimmune Diseases*
MicroRNAs* / genetics
Tumor Necrosis Factor-alpha / pharmacology
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Resource |
Human and Animal Cells |
MH7A(RCB1512) |