title: Glibenclamide impairs responses of neutrophils against Burkholderia pseudomallei by reduction of intracellular glutathione.
abstract: The major risk factor for melioidosis, an infectious disease caused by B. pseudomallei, is diabetes mellitus. More than half of diabetic melioidosis patients in Thailand were prescribed glibenclamide. Recent evidence demonstrates that glibenclamide reduces pro-inflammatory cytokine production by polymorphonuclear neutrophils (PMNs) of diabetic individuals in response to this bacterial infection. However, the mechanisms by which glibenclamide affects cytokine production are unknown. We found that PMNs from glibenclamide-treated diabetic individuals infected with live B. pseudomallei in vitro showed lower free glutathione (GSH) levels compared with those of healthy individuals. Glibenclamide decreased GSH levels and glutathione peroxidase (GPx) of PMNs after exposed to live B. pseudomallei. Moreover, glibenclamide reduced cytokine production and migration capacity of infected PMNs, whereas GSH could restore these functions. Taken together, our data show a link between the effect of glibenclamide on GSH and PMN functions in response to B. pseudomallei that may contribute to the susceptibility of diabetic individuals to B. pseudomallei infection.
authors.affiliation: The Centre for Research &Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors.forename: Chidchamai
authors.initials: C
authors.lastname: Kewcharoenwong
authors.affiliation: The Centre for Research &Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.affiliation: The Centre for Research &Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors.forename: Arnone
authors.initials: A
authors.lastname: Nithichanon
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, UK.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.affiliation: The Centre for Research &Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D016957:Burkholderia pseudomallei / Q000187:drug effects / Q000472:pathogenicity*; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology*; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008554:Melioidosis / Q000188:drug therapy / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D005978:Glutathione; D005905:Glyburide; D000111:Acetylcysteine