Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection

Kewcharoenwong, Chidchamai; Rinchai, Darawan; Utispan, Kusumawadee; Suwannasaen, Duangchan; Bancroft, Gregory J.; Ato, Manabu; Lertmemongkolchai, Ganjana

doi:10.1038/srep03363

Cited by 42 publications

(40 citation statements)

References 41 publications

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“…Our previous studies and those of others in diabetes mellitus patients have described defects in PMN phagocytosis, migration, and oxidative burst responses to kill B. pseudomallei (28), as well as reductions in proinflammatory cytokines (40) and dysfunction in Th1 cell responses to B. pseudomallei infection (41). We report in this article that increased PD-L1 expression on B. pseudomallei-infected PMNs correlated with increasing T cell dysfunction in type 2 diabetic patients.…”

Section: Discussionsupporting

confidence: 58%

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Buddhisa

Rinchai

Ato

et al. 2015

The Journal of Immunology

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Polymorphonuclear neutrophils (PMNs) are terminally differentiated cells that are involved in innate immune responses and form an early line of defense against pathogens. More recently, it has been shown that PMNs have immunosuppressive abilities on other immune cells. However, the effect of PMNs on T cell responses during bacterial infection remains to be determined. In this report, we examined the interaction of PMNs and T cells in response to infection with Burkholderia pseudomallei, the causative agent of human melioidosis. We observed that CD4+ T cell proliferation and IFN-γ production in response to polyclonal activators is significantly inhibited by uninfected PMNs, and to a greater extent B. pseudomallei–infected PMNs. Programmed death ligand 1 (PD-L1), a known regulator of T cell activation, is increased in mRNA expression in the blood of patients and upon infection of PMNs in vitro. The increased expression of PD-L1 was correlated with the degree of T cell inhibition in individuals with type 2 diabetes, a major risk factor of melioidosis. In vitro, addition of anti–PD-L1 Abs blocked this inhibitory activity and restored proliferation of CD4+ T cells and IFN-γ production, suggesting that PD-L1 on B. pseudomallei–infected PMNs is a regulatory molecule for the functions of T cells and may be involved in pathogenesis versus control of melioidosis.

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Section: Discussionsupporting

confidence: 58%

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Buddhisa

Rinchai

Ato

et al. 2015

The Journal of Immunology

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“…Diabetes‐induced functional defects in neutrophil responses to B. pseudomallei include impairments in phagocytosis, bacterial killing, neutrophil migration, cytokine production, apoptosis and NET formation . Diabetes was also associated with attenuated lipopolysaccharide‐induced cytokine responses, coinciding with reduced up‐regulation of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1, required for leucocyte transmigration into tissue .…”

Section: Effect Of Diabetes On the Early Immune Response To Intracellmentioning

confidence: 99%

Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections

et al. 2015

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SummaryDiabetes has been recognized as an important risk factor for a variety of intracellular bacterial infections, but research into the dysregulated immune mechanisms contributing to the impaired host-pathogen interactions is in its infancy. Diabetes is characterized by a chronic state of lowgrade inflammation due to activation of pro-inflammatory mediators and increased formation of advanced glycation end products. Increased oxidative stress also exacerbates the chronic inflammatory processes observed in diabetes. The reduced phagocytic and antibacterial activity of neutrophils and macrophages provides an intracellular niche for the pathogen to replicate. Phagocytic and antibacterial dysfunction may be mediated directly through altered glucose metabolism and oxidative stress. Furthermore, impaired activation of natural killer cells contributes to decreased levels of interferon-c, required for promoting macrophage antibacterial mechanisms. Together with impaired dendritic cell function, this impedes timely activation of adaptive immune responses. Increased intracellular oxidation of antigen-presenting cells in individuals with diabetes alters the cytokine profile generated and the subsequent balance of T-cell immunity. The establishment of acute intracellular bacterial infections in the diabetic host is associated with impaired T-cell-mediated immune responses. Concomitant to the greater intracellular bacterial burden and potential cumulative effect of chronic inflammatory processes, late hyper-inflammatory cytokine responses are often observed in individuals with diabetes, contributing to systemic pathology. The convergence of intracellular bacterial infections and diabetes poses new challenges for immunologists, providing the impetus for multidisciplinary research.

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“…Therefore, targeting these channels by sulfonylureas may reduce inflammation and inflammation-dependent injury (Cai et al, 2014;Ji, Yang, Ju, Zhu, & Yang, 2014). In addition, sulfonylureas can suppress cytokine production from activated macrophages by blocking the K + channels (Kewcharoenwong et al, 2013;Pompermayer et al, 2005), though this may increase potentially the risk of infection in DM (Kewcharoenwong et al, 2013). Cui et al (2015) demonstrated that glibenclamide reduced inflammation in lung tissue by suppression of T-helper Type 2 cytokines, vascular cell adhesion molecule-1 (VCAM-1), and phosphorylated signal transducer and activator of transcription 6 (p-STAT6).…”

Section: Sulfonylureasmentioning

confidence: 99%

A review of the anti‐inflammatory properties of antidiabetic agents providing protective effects against vascular complications in diabetes

Yaribeygi

Atkin

Pirro

et al. 2018

Journal Cellular Physiology

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The global prevalence of Type 2 diabetes mellitus and its associated complications are growing rapidly. Although the role of hyperglycemia is well recognized in the pathophysiology of diabetic complications, its exact underlying mechanisms are not fully understood. In this regard, accumulating evidence suggests that the role of inflammation appears pivotal, with studies showing that most diabetic complications are associated with an inflammatory response. Several classes of antidiabetic agents have been introduced for controlling glycemia, with evidence that these pharmacological agents may have modulatory effects on inflammation beyond their glucose‐lowering activity. Here we review the latest evidence on the anti‐inflammatory effects of commonly used antidiabetic medications and discuss the relevance of these effects on preventing diabetic complications.

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Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection

Cited by 42 publications

References 41 publications

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections

A review of the anti‐inflammatory properties of antidiabetic agents providing protective effects against vascular complications in diabetes

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