Cyclic GMP-dependent protein kinase II is necessary for inflammatory cytokine releases under monosodium urate exposure

期刊連結：http://www.gouthyperuricemia.com

Objective
Cyclic GMP-dependent protein kinase II (cGKII; PRKG2) has been identified as a gout-associated gene. In this study, we investigated the roles of cGKII in inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) release under monosodium urate (MSU) stimulation.
Methods
Using cGKII RNA interference (RNAi) method, we detected IL-6 and TNF-α release by ELISA, as well as cGKII and suppressor of cytokine signaling 1 (SOCS1) gene expression by real-time quantitative PCR.
Results
After 2 days of MSU treatment (7.0 and 10.5 mg/dl), the IL-6 release from human THP-1 monocyte/macrophage cell line was significantly increased. After 3 days of MSU treatment, the TNF-α release was also increased in THP-1 cells. In cGKII RNAi THP-1 cells, these MSU-induced inflammatory cytokine increases were significantly inhibited, indicating that cGKII positively regulates MSU-induced IL-6 and TNF-α releases. We further found that MSU enhanced cGKII gene expression after 3-5 days of treatments but not in days 1 and 2, similar to the time window of increased cytokines. In contrast, MSU enhanced immune-suppressive gene SOCS1 expression after 1-2 days of treatment, but not in days 3-5. This controversial SOCS1 expression was not observed in cGKII RNAi cells. These findings showed that cGKII negatively regulates SOCS1 expression.
Conclusion
Our study showed that cGKII positively regulates MSU-induced inflammatory cytokine IL-6 and TNF-α releases but negatively regulates immune-suppressive gene SOCS1 expression, indicating that cGKII is as an inflammatory enhancer under high MSU conditions, such as gouty inflammation.