Impaired inflammatory responses to multiple Toll-like receptor ligands in alveolar macrophages of streptozotocin-induced diabetic mice

Yamasawa, Hideaki; Nakayama, Masayuki; Bando, Masashi; Sugiyama, Yukihiko

doi:10.1007/s00011-011-0426-2

Cited by 10 publications

(9 citation statements)

References 48 publications

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“…Our preliminary data suggested that the hyperglycemic state impairs the reactivity of alveolar macrophages to selective TLR ligands, TLR2 ligand (PGN), and TLR5 ligand (FLG), by inhibiting the production of TNF-α [14]. Additionally, in the present study, the suppressed TNF-α production from alveolar macrophages in mice stimulated with PGN or FLG was alleviated by TJ-41.…”

Section: Discussionsupporting

confidence: 58%

Effect of Hochuekkito on Alveolar Macrophage Inflammatory Responses in Hyperglycemic Mice

et al. 2012

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Diabetes mellitus reduces immunological activity and increases susceptibility to various infections. Hochuekkito (TJ-41) has been reported to improve the weakened physical condition of various chronic diseases. BALB/c mice were divided into three groups; groups A and B were fed a standard diet, and group C, a TJ-41 diet. Two weeks after starting these diets, hyperglycemia was induced in groups B and C by injection with streptozotocin. Two weeks later, bronchoalveolar lavage was performed. Toll-like receptor (TLR) ligands (TLR2: peptidoglycan, PGN; TLR4: lipopolysaccharide, LPS; TLR5: flagellin, FLG) were used to stimulate alveolar macrophages (AMs), and TNF-α production was measured. Under hyperglycemic conditions and PGN or FLG stimulation, TNF-α production from AMs was significantly reduced in group B compared with group A. However, treatment with TJ-41 (group C) significantly improved the impaired production of TNF-α. These results suggest that, under hyperglycemic conditions, TJ-41 can improve the inflammatory responses of AMs with stimulation of TLR ligands.

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Section: Discussionsupporting

confidence: 58%

Effect of Hochuekkito on Alveolar Macrophage Inflammatory Responses in Hyperglycemic Mice

et al. 2012

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“…Insulin is reported to enhance glycolytic activity in rat macrophages (21), and attenuated cytokine production was described in AM from hyperglycemic diabetic rats (22), suggesting that defects in macrophage insulin signaling may contribute to reduced glycolysis-mediated antimycobacterial functions.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication

Gleeson

Sheedy

Pålsson-McDermott

et al. 2016

The Journal of Immunology

263

288

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Recent advances in immunometabolism link metabolic changes in stimulated macrophages to production of IL-1β, a crucial cytokine in the innate immune response to Mycobacterium tuberculosis. To investigate this pathway in the host response to M. tuberculosis, we performed metabolic and functional studies on human alveolar macrophages, human monocyte-derived macrophages, and murine bone marrow–derived macrophages following infection with the bacillus in vitro. M. tuberculosis infection induced a shift from oxidative phosphorylation to aerobic glycolysis in macrophages. Inhibition of this shift resulted in decreased levels of proinflammatory IL-1β and decreased transcription of PTGS2, increased levels of anti-inflammatory IL-10, and increased intracellular bacillary survival. Blockade or absence of IL-1R negated the impact of aerobic glycolysis on intracellular bacillary survival, demonstrating that infection-induced glycolysis limits M. tuberculosis survival in macrophages through induction of IL-1β. Drugs that manipulate host metabolism may be exploited as adjuvants for future therapeutic and vaccination strategies.

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“…Extending the in vitro experiments using cell lines and isolated splenic macrophages, there has been an ex vivo study examining the effects of hyperglycemia on alveolar macrophage function [25]. In contrast to studies using cell lines, hyperglycemia significantly decreased the respiratory burst of alveolar macrophages and impaired proinflammatory cytokine secretion, such as TNF- α and IL-6.…”

Section: Hyperglycemia and Innate Immune Cellsmentioning

confidence: 99%

“…It also demonstrated a reduced response to multiple TLR ligands in alveolar macrophages. The impaired reactivity of alveolar macrophage to TLR ligands might result from HG-induced alteration of intracellular signaling and is unlikely due to the modulation of TLR expression itself [25]. Hyperglycemia also promotes the inflammatory response by activating the NF- κ B pathway.…”

Section: Hyperglycemia and Innate Immune Cellsmentioning

confidence: 99%

Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

Xiu

Stanojcic

et al. 2014

International Journal of Endocrinology

116

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Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

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Impaired inflammatory responses to multiple Toll-like receptor ligands in alveolar macrophages of streptozotocin-induced diabetic mice

Abstract: Hyperglycemic state impairs the reactivity of AMs to multiple TLR ligands. This effect might result from hyperglycemia-induced alteration of intracellular signaling and is unlikely due to the modulation of TLR expression.

Cited by 10 publications

References 48 publications

Effect of Hochuekkito on Alveolar Macrophage Inflammatory Responses in Hyperglycemic Mice

Effect of Hochuekkito on Alveolar Macrophage Inflammatory Responses in Hyperglycemic Mice

Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication

Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

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