Sodium tungstate modulates inflammatory cytokine response in burkholderia pseudomallei -infected mice via inhibition of glycogen synthase kinase-3β

Anderson Tan, Mohammed Noor Embi, Suhaini Sudi, Hasidah Mohd. Sidek

Research output: Contribution to journalArticle

Abstract

Melioidosis, caused by Burkholderia pseudomallei is associated with high mortality due to overwhelming inflammatory response leading to septicaemia. Glycogen synthase kinase-3β (GSK3β) plays a central role in the regulation of pathogen-induced inflammatory response through modulation of pro- and anti-inflammatory cytokine production. Previous findings from our laboratory demonstrated that treatment with LiCL, a GSK3 inhibitor modulated the cytokine balance in B. pseudomallei-infected mice and increased animal survivability. Another inorganic salt, sodium tungstate (Na2WO4) which can induce ERK activation and trigger GSK3β phosphorylation also regulates the expression and secretion of pro- and anti-inflammatory cytokines. Here we extend our study to evaluate effects of Na2WO4 administration on the cytokine response towards B. pseudomallei infection in mice to reiterate involvement of GSK3β inhibition in modulating cytokine production in melioidosis. Pre-treatment with 100 mg/kg body weight Na2WO4 improved survivability (33.3 %) of B. pseudomallei-challenged mice (p<0.05). However, bacterial counts in liver and spleen of na2wo4-treated mice were not significantly different from that in non-treated controls. NA2WO4 administration resulted in increased phosphorylation of GSK3β in both liver and spleen samples by 2.2 and 3.3 fold respectively (p<0.05) compared to controls. Levels of pro-inflammatory cytokines, TNF-α and IFN-γ in sera of infected animals administered with Na2WO4 decreased by 15% whilst, the levels of anti-inflammatory cytokine, il-10 was elevated by 45% (p<0.05). Overall, the present findings reiterate our notion that inhibition of GSK3β, at least in part modulated the production of inflammatory cytokines induced during B. pseudomallei infection thus conferring survival advantage in infected animals tested.

Original languageEnglish
Pages (from-to)4-10
Number of pages7
JournalMalaysian Journal of Biochemistry and Molecular Biology
Volume19
Issue number1-2
Publication statusPublished - 1 Aug 2016

Fingerprint

Burkholderia pseudomallei
Glycogen Synthase Kinase 3
Cytokines
Burkholderia Infections
Melioidosis
Phosphorylation
Animals
Anti-Inflammatory Agents
Liver
Spleen
sodium tungstate(VI)
Bacterial Load
Pathogens
Sepsis
Salts
Chemical activation
Body Weight
Modulation
Mortality

Keywords

  • Burkholderia pseudomallei
  • Glycogen synthase kinase-3β (GSK3β)
  • Inflammation
  • Melioidosis
  • Sodium tungstate (NaWO)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

@article{b52d7b7a137c457bb8dacdbfc5499063,
title = "Sodium tungstate modulates inflammatory cytokine response in burkholderia pseudomallei -infected mice via inhibition of glycogen synthase kinase-3β",
abstract = "Melioidosis, caused by Burkholderia pseudomallei is associated with high mortality due to overwhelming inflammatory response leading to septicaemia. Glycogen synthase kinase-3β (GSK3β) plays a central role in the regulation of pathogen-induced inflammatory response through modulation of pro- and anti-inflammatory cytokine production. Previous findings from our laboratory demonstrated that treatment with LiCL, a GSK3 inhibitor modulated the cytokine balance in B. pseudomallei-infected mice and increased animal survivability. Another inorganic salt, sodium tungstate (Na2WO4) which can induce ERK activation and trigger GSK3β phosphorylation also regulates the expression and secretion of pro- and anti-inflammatory cytokines. Here we extend our study to evaluate effects of Na2WO4 administration on the cytokine response towards B. pseudomallei infection in mice to reiterate involvement of GSK3β inhibition in modulating cytokine production in melioidosis. Pre-treatment with 100 mg/kg body weight Na2WO4 improved survivability (33.3 {\%}) of B. pseudomallei-challenged mice (p<0.05). However, bacterial counts in liver and spleen of na2wo4-treated mice were not significantly different from that in non-treated controls. NA2WO4 administration resulted in increased phosphorylation of GSK3β in both liver and spleen samples by 2.2 and 3.3 fold respectively (p<0.05) compared to controls. Levels of pro-inflammatory cytokines, TNF-α and IFN-γ in sera of infected animals administered with Na2WO4 decreased by 15{\%} whilst, the levels of anti-inflammatory cytokine, il-10 was elevated by 45{\%} (p<0.05). Overall, the present findings reiterate our notion that inhibition of GSK3β, at least in part modulated the production of inflammatory cytokines induced during B. pseudomallei infection thus conferring survival advantage in infected animals tested.",
keywords = "Burkholderia pseudomallei, Glycogen synthase kinase-3β (GSK3β), Inflammation, Melioidosis, Sodium tungstate (NaWO)",
author = "Anderson Tan and Embi, {Mohammed Noor} and Suhaini Sudi and {Mohd. Sidek}, Hasidah",
year = "2016",
month = "8",
day = "1",
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volume = "19",
pages = "4--10",
journal = "Malaysian Journal of Biochemistry and Molecular Biology",
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TY - JOUR

T1 - Sodium tungstate modulates inflammatory cytokine response in burkholderia pseudomallei -infected mice via inhibition of glycogen synthase kinase-3β

AU - Tan, Anderson

AU - Embi, Mohammed Noor

AU - Sudi, Suhaini

AU - Mohd. Sidek, Hasidah

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Melioidosis, caused by Burkholderia pseudomallei is associated with high mortality due to overwhelming inflammatory response leading to septicaemia. Glycogen synthase kinase-3β (GSK3β) plays a central role in the regulation of pathogen-induced inflammatory response through modulation of pro- and anti-inflammatory cytokine production. Previous findings from our laboratory demonstrated that treatment with LiCL, a GSK3 inhibitor modulated the cytokine balance in B. pseudomallei-infected mice and increased animal survivability. Another inorganic salt, sodium tungstate (Na2WO4) which can induce ERK activation and trigger GSK3β phosphorylation also regulates the expression and secretion of pro- and anti-inflammatory cytokines. Here we extend our study to evaluate effects of Na2WO4 administration on the cytokine response towards B. pseudomallei infection in mice to reiterate involvement of GSK3β inhibition in modulating cytokine production in melioidosis. Pre-treatment with 100 mg/kg body weight Na2WO4 improved survivability (33.3 %) of B. pseudomallei-challenged mice (p<0.05). However, bacterial counts in liver and spleen of na2wo4-treated mice were not significantly different from that in non-treated controls. NA2WO4 administration resulted in increased phosphorylation of GSK3β in both liver and spleen samples by 2.2 and 3.3 fold respectively (p<0.05) compared to controls. Levels of pro-inflammatory cytokines, TNF-α and IFN-γ in sera of infected animals administered with Na2WO4 decreased by 15% whilst, the levels of anti-inflammatory cytokine, il-10 was elevated by 45% (p<0.05). Overall, the present findings reiterate our notion that inhibition of GSK3β, at least in part modulated the production of inflammatory cytokines induced during B. pseudomallei infection thus conferring survival advantage in infected animals tested.

AB - Melioidosis, caused by Burkholderia pseudomallei is associated with high mortality due to overwhelming inflammatory response leading to septicaemia. Glycogen synthase kinase-3β (GSK3β) plays a central role in the regulation of pathogen-induced inflammatory response through modulation of pro- and anti-inflammatory cytokine production. Previous findings from our laboratory demonstrated that treatment with LiCL, a GSK3 inhibitor modulated the cytokine balance in B. pseudomallei-infected mice and increased animal survivability. Another inorganic salt, sodium tungstate (Na2WO4) which can induce ERK activation and trigger GSK3β phosphorylation also regulates the expression and secretion of pro- and anti-inflammatory cytokines. Here we extend our study to evaluate effects of Na2WO4 administration on the cytokine response towards B. pseudomallei infection in mice to reiterate involvement of GSK3β inhibition in modulating cytokine production in melioidosis. Pre-treatment with 100 mg/kg body weight Na2WO4 improved survivability (33.3 %) of B. pseudomallei-challenged mice (p<0.05). However, bacterial counts in liver and spleen of na2wo4-treated mice were not significantly different from that in non-treated controls. NA2WO4 administration resulted in increased phosphorylation of GSK3β in both liver and spleen samples by 2.2 and 3.3 fold respectively (p<0.05) compared to controls. Levels of pro-inflammatory cytokines, TNF-α and IFN-γ in sera of infected animals administered with Na2WO4 decreased by 15% whilst, the levels of anti-inflammatory cytokine, il-10 was elevated by 45% (p<0.05). Overall, the present findings reiterate our notion that inhibition of GSK3β, at least in part modulated the production of inflammatory cytokines induced during B. pseudomallei infection thus conferring survival advantage in infected animals tested.

KW - Burkholderia pseudomallei

KW - Glycogen synthase kinase-3β (GSK3β)

KW - Inflammation

KW - Melioidosis

KW - Sodium tungstate (NaWO)

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M3 - Article

VL - 19

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EP - 10

JO - Malaysian Journal of Biochemistry and Molecular Biology

JF - Malaysian Journal of Biochemistry and Molecular Biology

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