ABSTRACT
OBJECTIVES@#To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis (RA).@*METHODS@#A total of 36 patients with RA were selected, peripheral blood mononuclear cell (PBMC) and granulocyte were separated from venous blood. RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patients with RA, and detect the mRNA expression of downstream factor IL-1α. The correlation between RA and the expression of NLRP3 and NLRP1 was analyzed. Normal 30 cases were set as control group.@*RESULTS@#Expression levels of NLRP1, and caspase-1 mRNA in PBMC of RA group were significantly lower than those of control group (P0.05); NLRP3, caspase-1, and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group (P0.05); NLRP1, IL-1α mRNA expression level had a negative correlation with anti-rheumatoid factor antibody (P=0.033 2, 0.034 0).@*CONCLUSIONS@#NLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors, and play an important role in RA inflammatory mechanisms.
ABSTRACT
<p><b>BACKGROUND</b>Reactive oxygen species (ROS) may play both physiological and pathophysiological roles. Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response element (ARE)-mediated genes expression and coordinates induction of chemoprotective proteins in response to physical and chemical stresses. The exact role of Nrf2 in cellular responses to different levels of oxidative stresses remains unknown.</p><p><b>METHODS</b>Rat pulmonary microvascular endothelial cells were cultured and treated with 0 mmol/L, 0.125 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L hydrogen peroxide solution for 2 hours. Nrf2 gene expression was assayed by reverse transcription-PCR, Nrf2-ARE binding activity was assayed with electrophoretic mobility shift assay (EMSA), and localization of Nrf2 was detected with immunohistochemistry.</p><p><b>RESULTS</b>Low and moderate (0.125 mmol/L, 0.25 mmol/L and 0.5 mmol/L) doses hydrogen peroxide exposure of rat pulmonary microvascular endothelial cells led to the nuclear accumulation of Nrf2, increased activity of transcription regulation and up-regulation of ARE-medicated gene expression. In contrast, high doses of hydrogen peroxide (1 mmol/L, 2 mmol/L) exposure of the cells led to the nuclear exclusion of Nrf2, decreased activity transcription regulation and down-regulation of ARE-mediated gene expression.</p><p><b>CONCLUSION</b>Low and moderate doses of hydrogen peroxide play protective roles by increasing transcription activity of Nrf2, whereas high- dose hydrogen peroxide plays a deleterious role by decreasing transcription activity of Nrf2.</p>