MALT-1 inhibition attenuates the inflammatory response of ankylosing spondylitis by targeting NF-κB activation

Abstract

Background: The present study aimed to investigate the effects of mucosa-associated lymphoid tissue lymphoma translocation protein (MALT)-1 on ankylosing spondylitis and its underlying mechanisms.

Methods: Proteoglycan induced ankylosing spondylitis (PGIA) mouse model was established and the expression patterns of MALT-1 were determined in joint tissue. Next, the mice were intraarticularly administrated with MALT-1 in the PGIA mouse model. Meanwhile, shRNA was intraarticularly administrated to PGIA mice. The incidence of arthritis and clinical score was evaluated. Besides, the levels of inflammatory cytokines and matrix metalloproteinases (MMPs) were measured. Protein expressions of full-length CYLD (FL-CYLD), C-terminal cleavage fragment (CYLD-CL), and nuclear factor (NF)-κB were determined.

Results: The mRNA and protein levels of MALT1 were increased in the PGIA mouse model. The treatment of MALT-1 accelerated arthritis incidence and joint damage, whereas shMALT-1 suppressed arthritis symptoms in the PGIA mouse model. In addition, treatment of shMALT-1 suppressed the levels of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β), MMP-3, and MMP-9. Furthermore, the treatment of shMALT-1 suppressed the levels of CYLD and NF-κB in the joint tissues in the PGIA mouse model.

Conclusion: The inhibition of MALT-1 suppressed the inflammatory response in ankylosing spondylitis in part by the regulation of CYLD and NF-κB.

Keywords: Ankylosing Spondylitis; Arthritis; Inflammation; MALT-1; NF-κB activation.