Tripartite Motif-containing 22 Is Involved in TLR3-mediated Inflammatory Pathway in Rheumatoid Fibroblast-like...

Area of Science:

• Immunology
• Molecular Biology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is an autoimmune disease causing synovial inflammation and cartilage damage.
• Tripartite motif-containing 22 (TRIM22) is an E3 ubiquitin ligase involved in immunity and signal transduction.
• The role of TRIM22 in RA synovial inflammation requires further investigation.

Purpose of the Study:

• To investigate TRIM22 expression in rheumatoid arthritis.
• To explore the regulatory pathways of TRIM22 in response to inflammatory stimuli.
• To determine the functional role of TRIM22 in synovial inflammation.

Main Methods:

• Cultured human rheumatoid fibroblast-like synoviocytes (RFLS) stimulated with polyinosinic:polycytidylic acid (poly I:C), a TLR3 ligand.
• RNA interference (siRNA) to knockdown TRIM22, interferon-β (IFN-β), and nuclear factor-kappa B (NF-κB) p65.
• Immunohistochemistry to assess TRIM22 expression in RA and osteoarthritis synovial tissues.

Main Results:

• Poly I:C upregulated TRIM22 expression in RFLS in a dose- and time-dependent manner.
• TRIM22 expression was modulated by IFN-β and NF-κB pathways.
• TRIM22 knockdown reduced poly I:C-induced C-C motif chemokine ligand 5 (CCL5) and IFN-β expression.
• Elevated TRIM22 expression was observed in RA synovial tissue compared to osteoarthritis.

Conclusions:

• TLR3 agonist stimulation upregulates TRIM22 in RFLS.
• TRIM22 is regulated by IFN-β and NF-κB pathways.
• TRIM22 positively influences poly I:C-induced CCL5 and IFN-β expression, indicating a potential role in RA synovial inflammation.