Effects of Tyrosine Kinase Signaling Inhibition on Survival After Cecal Ligation and Puncture in Diet‐Restricted Mice

Kang, Woodae; Saito, Hideaki; Fukatsu, Kazuhiko; Hidemura, Akio; Koyama, Hiroyuki; Sakamoto, Tetsuya; Maekawa, Kazuyuki

doi:10.1177/0148607101025006291

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…Early studies by Kang et al . reported increased mortality after CLP-induced sepsis in mice under 50-75% DR compared to AL mice (18, 19). Another study by Bermudes et al .…”

Section: Discussionmentioning

confidence: 99%

Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

Starr

Steele

Cohen

et al. 2016

Critical Care Medicine

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Objective Visceral adipose tissue is a major site for expression of pro-inflammatory and pro-coagulant genes during acute systemic inflammation. In this study, we tested whether loss of fat mass by dietary restriction (DR) would remove the major source of these factors resulting in improved tolerance to sepsis and endotoxemia. Design Prospective, laboratory controlled experiments. Setting Aging and Critical Care Research Laboratory in a university hospital. Subjects Middle-aged (12 month-old) male C57BL/6 mice. Interventions Mice were subjected to 40% DR for three weeks followed by induction of abdominal sepsis or endotoxemia by intraperitoneal injection with cecal slurry or lipopolysaccharide (LPS), respectively. Measurements and main results Compared to freely-fed mice, DR mice exhibited dramatically improved survival (80% vs 0% after sepsis, p<0.001;86% vs 12%after endotoxemia, p=0.013) and significantly reduced visceral fat-derived mRNA expression of interleukin-6 (IL-6), thrombospondin-1, plasminogen activator inhibitor-1, and tissue factor which positively correlated with fat mass. Plasma levels of IL-6 were significantly reduced by DR and correlated with adipose IL-6 mRNAlevels and fat mass (p<0.001, R2=0.64 and 0.89). In vitro culture of visceral fat explants from naïve DR mice showed significantly reduced IL-6 secretion compared to that from freely-fed mice in response to LPS. Analysis of major adipose immune cell populations by flow cytometry demonstrated that macrophages were the only cell population reduced by DR and that CD11c+/CD206+ (M2-type) and CD11c-/CD206- (double negative) macrophages, in addition to T cells, are the major immune cell populations that produce IL-6 in middle-age during systemic inflammation. Conclusions Short-term DR drastically improved the survival outcome of middle-aged mice during both polymicrobial sepsis and sterile endotoxemia. Improved survival was accompanied by a significantly attenuated inflammatory response in adipose tissue, which is likely due to alterations of both fat mass quantity and qualitative changes including a reduction in macrophage populations.

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“…Early studies by Kang et al . reported increased mortality after CLP-induced sepsis in mice under 50-75% DR compared to AL mice (18, 19). Another study by Bermudes et al .…”

Section: Discussionmentioning

confidence: 99%

Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

Starr

Steele

Cohen

et al. 2016

Critical Care Medicine

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“…13 We previously demonstrated tyrosine phosphorylation events and the activity of ERK, a MAPK subfamily, in PRCs after exposure to inflammatory stimuli blunted by severe dietary restriction. 3,4 Thus, nutritional replenishment may restore NFB activation by re-establishing the activities of these upstream signaling events.…”

Section: May-june 2003mentioning

confidence: 99%

“…2 Intracellular signaling molecules regulate the production of proinflammatory cytokines and chemokines by immune cells. 3 Severe dietary restriction reportedly impairs the activation of signaling molecules including tyrosine kinase and extracellular signal-regulated kinase in resident peritoneal macrophages and exudative neutrophils. 3,4 Among signaling molecules, nuclear factor B (NFB) is a key regulator of host defense.…”

mentioning

confidence: 99%

“…3 Severe dietary restriction reportedly impairs the activation of signaling molecules including tyrosine kinase and extracellular signal-regulated kinase in resident peritoneal macrophages and exudative neutrophils. 3,4 Among signaling molecules, nuclear factor B (NFB) is a key regulator of host defense. 5 NFB is a ubiquitous transcription factor that plays critical roles in inflammatory and immune responses such as gene expression of proinflammatory cytokines, chemokines, and adhesion molecules.…”

mentioning

confidence: 99%

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Brief refeeding rapidly reverses dietary restriction‐induced nuclear factor‐kappaB downregulation in peritoneal resident cells

Kang

Saito²,

Fukatsu³

et al. 2003

J Parenter Enteral Nutr

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Calorie restriction increases the sensitivity of progeroid Ercc1Δ/− mice to acute (neuro)inflammation

Reitsema,

Schreuder,

Gerrits

et al. 2024

GeroScience

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Hospitalized elderly patients frequently suffer from delirium, especially in the context of sepsis-associated encephalopathy. Current treatments of delirium are merely symptomatic. Calorie restriction (CR) is both a promising strategy to protect against sepsis and has beneficial effects on aging-induced neurodegeneration. In this study, we investigated whether six weeks of 30% CR had protective effects on lipopolysaccharide (LPS) induced (neuro)inflammation in wild-type (WT) and progeroid mice deficient in the DNA excision-repair gene Ercc1 (Ercc1Δ/−). While CR did not affect the LPS-induced inflammatory response in WT mice, CR exaggerated the peripheral inflammatory response in Ercc1Δ/− mice, as evidenced by an increase of pro-inflammatory serum cytokines (TNF-α, IL-1β, and IFN-γ) and kidney injury marker Ngal. Neuroinflammatory effects were assessed by RNA-sequencing of isolated microglia. Similarly, CR did not affect microglia gene expression in WT mice, but increased neuroinflammation-associated gene expression in Ercc1Δ/− mice. In conclusion, CR increases the peripheral and brain inflammatory response of Ercc1Δ/− mice to a systemic inflammatory stimulus.

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Effects of Tyrosine Kinase Signaling Inhibition on Survival After Cecal Ligation and Puncture in Diet‐Restricted Mice

Cited by 8 publications

References 27 publications

Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

Brief refeeding rapidly reverses dietary restriction‐induced nuclear factor‐kappaB downregulation in peritoneal resident cells

Calorie restriction increases the sensitivity of progeroid Ercc1Δ/− mice to acute (neuro)inflammation

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