Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling

Yen, Wei-Chen; Wu, Yi-Hsuan; Wu, Chih-Ching; Lin, Hsin-Ru; Stern, Arnold; Chen, Shih-Hsiang; Shu, Jwu-Ching; Tsun-Yee Chiu, Daniel

Certain chronic and infectious diseases are associated with G6PD deficiency [13, 24, 43] . The impact of G6PD status on innate immunity, especially upon inflammasome activation, is unknown. The present study is the first to show that G6PD-kd THP-1 cells and PBMCs from patients with G6PD deficiency with different mutations of the enzyme have a decrease in IL-1β expression and NLRP3 inflammasome (E) c-Fos quantitative level of (D). β-Actin was used as a normalized loading control in (A) and (D). The results are representative of three independent experiments (n = 3, *p < 0.05). (F) Western blot of cytoplasmic and nuclear proteins. Cells were treated with LPS for 60 min. α-Tubulin and lamin B1 were used as cytoplasmic and nuclear loading controls. (G) c-Fos quantitative level of (F). The results are representative of three independent experiments (n = 3, *p < 0.05). (H) Luciferase activity assay of 293T cells transfected with a firefly luciferase reporter plasmid containing a partial sequence with the putative AP-1 binding site (WT) or the deleted mutation (AP1D). This assay was standardized by Renilla activity after transfection for 48 h (*p < 0.05 compared to basal conditions).