GSK3β inhibition confers survival advantage in Burkholderia pseudomallei-infected hyperglycaemic mice by regulating inflammatory response
Burkholderia pseudomallei, the etiologic agent of melioidosis is a common cause of sepsis mainly in diabetic individuals in South East Asia. Glycogen synthase kinase-3β (GSK3β) plays a pivotal role in modulating inflammatory balance in Gram-negative bacterial infections. In this study, we demonstrate that inhibition of GSK3β significantly improved survival of hyperglycaemic mice acutely infected with B. pseudomallei. With GSK3β inhibition, we found significant modulation between pro- (IL-12, TNF-alpha) and anti-inflammatory (IL10) serum cytokines which may have contributed to bacterial clearance in multiple organs of B. pseudomallei-infected hyperglycaemic mice. Concurrently, an increase in phosphorylation of GSK3β at Ser-9 was observed in the liver of B. pseudomallei-infected hyperglycaemic mice. Likewise, B. pseudomallei-infected non-hyperglycaemic mice upon GSK3β inhibition showed similar trends of bacterial clearance and modulation of serum cytokines; however, the effect of enhanced survival was less substantial than in infected hyperglycaemic mice. Taken together, we demonstrate that inhibition of GSK3β confers survival advantage of hyperglycaemic mice infected with B. pseudomallei and offers a potential therapeutic strategy for the treatment of diabetic patients with melioidosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Tropical biomedicine - 35(2018), 1 vom: 01. März, Seite 228-238 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Maniam, P [VerfasserIn] |
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| Themen: |
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| Anmerkungen: |
Date Revised 19.02.2021 published: Print Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Burkholderia pseudomallei, the etiologic agent of melioidosis is a common cause of sepsis mainly in diabetic individuals in South East Asia. Glycogen synthase kinase-3β (GSK3β) plays a pivotal role in modulating inflammatory balance in Gram-negative bacterial infections. In this study, we demonstrate that inhibition of GSK3β significantly improved survival of hyperglycaemic mice acutely infected with B. pseudomallei. With GSK3β inhibition, we found significant modulation between pro- (IL-12, TNF-alpha) and anti-inflammatory (IL10) serum cytokines which may have contributed to bacterial clearance in multiple organs of B. pseudomallei-infected hyperglycaemic mice. Concurrently, an increase in phosphorylation of GSK3β at Ser-9 was observed in the liver of B. pseudomallei-infected hyperglycaemic mice. Likewise, B. pseudomallei-infected non-hyperglycaemic mice upon GSK3β inhibition showed similar trends of bacterial clearance and modulation of serum cytokines; however, the effect of enhanced survival was less substantial than in infected hyperglycaemic mice. Taken together, we demonstrate that inhibition of GSK3β confers survival advantage of hyperglycaemic mice infected with B. pseudomallei and offers a potential therapeutic strategy for the treatment of diabetic patients with melioidosis | ||
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