The roles of SFKs in the regulation of proinflammatory cytokines and NLRP3 in familial mediterranean fever patients

Familial Mediterranean Fever (FMF) is caused by mutations in pyrin, a protein produced in innate immune cells that regulates the development of interleukin (IL)-1β by interacting with caspase-1 and other components of inflammasomes. Although overexpression of proinflammatory cytokines have been observed in FMF patients, no studies have been conducted on the role of Src family kinases (SFKs). The purpose of this study was to examine the impact of SFKs on the modulation of IL-1β, IL-6, IL-8, TNF-α, and NLRP3 inflammasome in patients with FMF. The study included 20 FMF patients and 20 controls. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. Protein expression levels of SFKs members were measured by western blot. The effect of lipopolysaccharide-induced (LPS) activation and PP2- induced inhibition of SFKs on NLRP3 and IL-1β, IL 6, IL-8, TNF-α were examined by western blot and flow cytometry respectively. Patients with FMF have considerably greater levels of Lck expression. In addition, patients had a substantially greater basal level of NLRP3 than the control group (*p = 0.016). Most importantly, the levels of IL-1 β were elevated with LPS stimulation and reduced with PP2 inhibition in FMF patients. These results suggest that SFKs are effective in regulation of IL-1 β in FMF patients.