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Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation : A potential cause of neutrophil dysfunction in chronic kidney disease

Olsson, Jenny LU ; Jacobson, Therese A S; Paulsson, Josefin M.; Dadfar, Elham; Moshfegh, Ali; Jacobson, Stefan H. and Lundahl, Joachim (2011) In Nephrology Dialysis Transplantation 26(7). p.2195-2201
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, IL-1R1, IL-1R2 and IL8RA gene expression... (More)

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, IL-1R1, 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-7- acetate (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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chemokines, chronic kidney disease, leucocyte dysfunction, respiratory burst, SOD2
in
Nephrology Dialysis Transplantation
volume
26
issue
7
pages
7 pages
publisher
Oxford University Press
external identifiers
  • scopus:79959929539
ISSN
0931-0509
DOI
10.1093/ndt/gfq673
language
English
LU publication?
yes
id
ed44688e-a8b7-4197-8e84-132a9974508b
date added to LUP
2016-11-21 11:45:54
date last changed
2017-11-19 04:34:59
@article{ed44688e-a8b7-4197-8e84-132a9974508b,
  abstract     = {<p>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, IL-1R1, 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-7- acetate (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.</p>},
  author       = {Olsson, Jenny and Jacobson, Therese A S and Paulsson, Josefin M. and Dadfar, Elham and Moshfegh, Ali and Jacobson, Stefan H. and Lundahl, Joachim},
  issn         = {0931-0509},
  keyword      = {chemokines,chronic kidney disease,leucocyte dysfunction,respiratory burst,SOD2},
  language     = {eng},
  number       = {7},
  pages        = {2195--2201},
  publisher    = {Oxford University Press},
  series       = {Nephrology Dialysis Transplantation},
  title        = {Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation : A potential cause of neutrophil dysfunction in chronic kidney disease},
  url          = {http://dx.doi.org/10.1093/ndt/gfq673},
  volume       = {26},
  year         = {2011},
}