Serum amyloid A triggers the MSU-mediated mature interleukin-1beta production from human synovial fibroblasts Full Text
Arthritis Research & Therapy, 05/21/2012
Migita K et al. – The data demonstrates that exposure of human synovial fibroblasts to serum amyloid A (SAA) promotes Monosodium urate (MSU)–mediated caspase–1 activation and IL–1beta secretion in the absence of microbial stimulation. These findings provide insight into the molecular processes underlying the synovial inflammatory condition of gout.Methods
- Human synovial fibroblasts were stimulated with MSU in the presence or absence of serum amyloid A (SAA).
- The cellular supernatants were analyzed by immunoblotting using anti–IL–1 or anti–caspase–1 antibodies.
- IL–1 or NLRP3 mRNA expressions were analyzed by real–time PCR or reverse transcription–PCR (RT–PCR) method.
- Neither SAA nor MSU stimulation resulted in IL–1beta or interleukin–1 (IL–1 secretions and pro–IL–1beta processing in synovial fibroblasts.
- However, in SAA–primed synovial fibroblasts, MSU stimulation resulted in the activation of caspase–1 and production of active IL–1beta and IL–1.
- The effect of SAA on IL–1beta induction was impaired in cells by silencing NLRP3 using siRNA or treating with caspase–1 inhibitor.
- In addition, SAA induced the secretion of cathepsin B and NLRP3 mRNA expression in synovial fibroblasts.