Back to Search
Start Over
Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation: a potential cause of neutrophil dysfunction in chronic kidney disease
- Source :
- Nephrology Dialysis Transplantation. 26:2195-2201
- Publication Year :
- 2010
- Publisher :
- Oxford University Press (OUP), 2010.
-
Abstract
- Background. Neutrophils from patients with chronic kidney disease (CKD) are dysfunctional and thus a contributing factor to the risk of infections. The mechanisms for leucocyte dysfunction in CKD are not fully understood. It is known that lipopolysaccharide (LPS) activates transcription of several genes encoding proinflammatory cytokines. We therefore aimed to study the effect of LPS on neutrophil expression of genes related to the inflammatory response to address the hypothesis that LPS-induced gene transcriptions are altered in CKD patients. Methods. We analysed gene expression of LPS-stimulated neutrophils from 30 patients with CKD and 15 healthy controls. Superoxide dismutase-2 (SOD2), IL1A, IL1R1, IL-1R2 and IL8RA gene expression from both neutrophils and differentiated HL60 cells were measured by quantitative polymerase chain reaction. Differentiated HL60 cells were stimulated with phorbol-12-myristate-7acetate (PMA) after inhibition of SOD2 by small interfering RNA followed by respiratory burst assessment using flow cytometry. Results. LPS stimulation induced a significant mobilization of CD11b on neutrophils from CKD and healthy controls. Upregulation of SOD2, IL1A, IL-1R1 and IL-1R2 gene expression in neutrophils from healthy controls after LPS stimulation was contrasted by no change in gene transcription (IL-1R1 and IL-1R2) or even a downregulation in patients with CKD (SOD2 and IL1A). Inhibition of SOD2 reduced the PMA-induced respiratory burst and IL1A, IL-1R1, IL-1R2 and IL8RA gene expression in neutrophil-differentiated HL60 cells. Conclusions. Because of the critical role of SOD2 in the generation of hydrogen peroxide during phagocytosis, downregulation of SOD2 gene expression after LPS stimulation in neutrophils from patients with CKD indicates a potential mechanism for neutrophil dysfunction and cytokine dysregulation in these patients.
- Subjects :
- Lipopolysaccharides
Male
medicine.medical_specialty
Chemokine
Neutrophils
medicine.medical_treatment
Blotting, Western
SOD2
Down-Regulation
HL-60 Cells
Interleukin 8 receptor, alpha
Proinflammatory cytokine
Internal medicine
Phorbol Esters
Gene expression
Humans
Medicine
RNA, Messenger
Cells, Cultured
Oligonucleotide Array Sequence Analysis
Respiratory Burst
Transplantation
biology
Reverse Transcriptase Polymerase Chain Reaction
Superoxide Dismutase
business.industry
Gene Expression Profiling
Cell Differentiation
Middle Aged
Respiratory burst
Endocrinology
Cytokine
IL1A
Nephrology
Case-Control Studies
Immunology
biology.protein
Kidney Failure, Chronic
Female
business
Biomarkers
Subjects
Details
- ISSN :
- 14602385 and 09310509
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Nephrology Dialysis Transplantation
- Accession number :
- edsair.doi.dedup.....5179ebb9f781b36347bbacc302a1a3c5
- Full Text :
- https://doi.org/10.1093/ndt/gfq673