Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling
| العنوان: | Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling |
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| المؤلفون: | Shih-Hsiang Chen, Chih-Ching Wu, Arnold Stern, Wei-Chen Yen, Hsin-Ru Lin, Daniel Tsun-Yee Chiu, Yi-Hsuan Wu, Jwu-Ching Shu |
| المصدر: | Redox Biology Redox Biology, Vol 28, Iss, Pp-(2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Lipopolysaccharides, Male, Lipopolysaccharide, THP-1 Cells, Clinical Biochemistry, Interleukin-1beta, AP-1, activator protein 1, G6PD, glucose-6-phosphate dehydrogenase, p38 Mitogen-Activated Protein Kinases, Biochemistry, Inflammasome, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Bactericidal response, NOS, nitric oxide synthase, lcsh:QH301-705.5, chemistry.chemical_classification, Gene knockdown, lcsh:R5-920, NADPH oxidase, biology, Chemistry, NADPH, reduced form of nicotinamide adenine dinucleotide phosphate, NOX, NADPH oxidase, Cell biology, G6PD-kd, G6PD knockdown, PBMC, peripheral blood mononuclear cells, IL-1β, H2O2, hydrogen peroxide, Gene Knockdown Techniques, Phosphorylation, Female, lcsh:Medicine (General), Redox homeostasis, medicine.drug, Research Paper, PMA, phorbol 12-myristate 13-acetate, Adult, congenital, hereditary, and neonatal diseases and abnormalities, ATP, adenosine triphosphate, Down-Regulation, 03 medical and health sciences, Young Adult, ROS, reactive oxygen species, parasitic diseases, medicine, Humans, Aged, Reactive oxygen species, NO, nitric oxide, Innate immune system, Organic Chemistry, UP-LPS, ultrapure lipopolysaccharide, nutritional and metabolic diseases, NADPH Oxidases, Transcription Factor AP-1, 030104 developmental biology, Glucosephosphate Dehydrogenase Deficiency, HEK293 Cells, lcsh:Biology (General), MAPK, mitogen-activated protein kinases, Case-Control Studies, biology.protein, THP-1, human monocytic cells, Leukocytes, Mononuclear, Adenosine triphosphate, 030217 neurology & neurosurgery, G6PD |
| الوصف: | Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH. G6PD-deficient cells have a reduced ability to induce the innate immune response, thus increasing host susceptibility to pathogen infections. An important part of the immune response is the activation of the inflammasome. G6PD-deficient peripheral blood mononuclear cells (PBMCs) from patients and human monocytic (THP-1) cells were used as models to investigate whether G6PD modulates inflammasome activation. A decreased expression of IL-1β was observed in both G6PD-deficient PBMCs and PMA-primed G6PD-knockdown (G6PD-kd) THP-1 cells upon lipopolysaccharide (LPS)/adenosine triphosphate (ATP) or LPS/nigericin stimulation. The pro-IL-1β expression of THP-1 cells was decreased by G6PD knockdown at the transcriptional and translational levels in an investigation of the expression of the inflammasome subunits. The phosphorylation of p38 MAPK and downstream c-Fos expression were decreased upon G6PD knockdown, accompanied by decreased AP-1 translocation into the nucleus. Impaired inflammasome activation in G6PD-kd THP-1 cells was mediated by a decrease in the production of reactive oxygen species (ROS) by NOX signaling, while treatment with hydrogen peroxide (H2O2) enhanced inflammasome activation in G6PD-kd THP-1 cells. G6PD knockdown decreased Staphylococcus aureus and Escherichia coli clearance in G6PD-kd THP-1 cells and G6PD-deficient PBMCs following inflammasome activation. These findings support the notion that enhanced pathogen susceptibility in G6PD deficiency is, in part, due to an altered redox signaling, which adversely affects inflammasome activation and the bactericidal response. Graphical abstract Image 1 |
| تدمد: | 2213-2317 |
| DOI: | 10.1016/j.redox.2019.101363 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07b360c05a34b1841e9dee64dd83226fTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....07b360c05a34b1841e9dee64dd83226f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2019.101363 |