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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.