Complement factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis

Area of Science:

• Immunology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints.
• Understanding the molecular mechanisms of RA inflammation is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the role and mechanism of Complement Factor H (CFH) in RA peripheral and joint inflammation.
• To identify potential therapeutic targets for RA.

Main Methods:

• ELISA to measure CFH levels in serum and synovial fluid.
• Western blotting and flow cytometry for monocyte pyroptosis.
• ELISA for inflammatory cytokine release.
• Wound healing and transwell assays for fibroblast-like synoviocyte (FLS) migration and invasion.
• RNA sequencing to identify CFH targets.

Main Results:

• CFH levels were elevated in RA patients and correlated with disease activity markers (hs-CRP, ESR, DAS28).
• CFH suppressed monocyte pyroptosis and inflammatory cytokine release (IL-1β, IL-6).
• CFH inhibited RA FLS migration, invasion, and TNF-α-induced inflammatory mediator production (IL-6, IL-8, MMPs).
• CFH upregulated eukaryotic translation initiation factor 3 (EIF3C) in RA monocytes and FLS.

Conclusions:

• CFH exhibits anti-inflammatory effects in RA peripheral and joint inflammation.
• CFH may serve as a potential therapeutic target for RA.