ABSTRACT
Familial Mediterranean Fever (FMF) is caused by mutations in pyrin, a protein produced in innate immune cells that regulates the development of interleukin (IL)-1ß 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-1ß, 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-1ß, 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 ß 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 ß in FMF patients.
Subject(s)
Cytokines , Familial Mediterranean Fever , NLR Family, Pyrin Domain-Containing 3 Protein , src-Family Kinases , Humans , Familial Mediterranean Fever/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Male , Female , Cytokines/metabolism , Adult , src-Family Kinases/metabolism , Lipopolysaccharides/pharmacology , Inflammasomes/metabolism , Leukocytes, Mononuclear/metabolism , Young Adult , Carrier Proteins/metabolism , Interleukin-1beta/metabolism , Inflammation Mediators/metabolismABSTRACT
OBJECTIVE: This study aimed to investigate the expression levels of sirtuin 2 and sirtuin 7 in the placenta accreta spectrum to reveal their role in its pathogenesis. METHODS: A total of 30 placenta accreta spectrum, 20 placenta previa, and 30 controls were experienced. The sirtuin 2 and sirtuin 7 expression levels in the placentas of these groups were determined by Western blot. sirtuin 2 and sirtuin 7 serum levels in the maternal and fetal cord blood were examined by enzyme-linked immunosorbent assay. RESULTS: It was found that sirtuin 7 in placenta accreta spectrum was significantly lower in the placenta compared to the control and placenta previa groups (p<0.05). However, a significant difference was not observed between the sirtuin 2 and sirtuin 7 levels in the maternal and fetal cord serum samples of those three groups (p>0.05). CONCLUSION: Sirtuin 7 may play an important role in the formation of placenta accreta spectrum. The effect of decreased expression of sirtuin 7 might be tissue-dependent in the placenta accreta spectrum and needs to be investigated further.
Subject(s)
Placenta Accreta , Placenta Previa , Pregnancy , Female , Humans , Placenta Accreta/metabolism , Placenta Previa/metabolism , Sirtuin 2/metabolism , Placenta/metabolism , Blotting, Western , Retrospective StudiesABSTRACT
SUMMARY OBJECTIVE: This study aimed to investigate the expression levels of sirtuin 2 and sirtuin 7 in the placenta accreta spectrum to reveal their role in its pathogenesis. METHODS: A total of 30 placenta accreta spectrum, 20 placenta previa, and 30 controls were experienced. The sirtuin 2 and sirtuin 7 expression levels in the placentas of these groups were determined by Western blot. sirtuin 2 and sirtuin 7 serum levels in the maternal and fetal cord blood were examined by enzyme-linked immunosorbent assay. RESULTS: It was found that sirtuin 7 in placenta accreta spectrum was significantly lower in the placenta compared to the control and placenta previa groups (p<0.05). However, a significant difference was not observed between the sirtuin 2 and sirtuin 7 levels in the maternal and fetal cord serum samples of those three groups (p>0.05). CONCLUSION: Sirtuin 7 may play an important role in the formation of placenta accreta spectrum. The effect of decreased expression of sirtuin 7 might be tissue-dependent in the placenta accreta spectrum and needs to be investigated further.
