High Glucose Environments Interfere with Bone Marrow-Derived Macrophage Inflammatory Mediator Release, the TLR4 Pathway and Glucose Metabolism

Ayala, Thais Soprani; Tessaro, Fernando Henrique Galvão; Jannuzzi, Grasielle Pereira; Bella, Leonardo Mendes; Ferreira, Karen Spadari; Martins, Joilson O.

doi:10.1038/s41598-019-47836-8

Cited by 50 publications

(62 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies in other vertebrates demonstrate that high glucose exposure results in an increased cytokine response of macrophages upon lipopolysaccharide exposure but reduces the overall phagocytic rate (47, 48). Our data provides evidence that there is a high glucose concentration in the central organs (brain and liver) of Pachón cavefish in all treatment groups (Fig 4), which leads us to the hypothesis that high glucose concentration is the main driver of the hypersensitivity and reduced phagocytic rate of innate immune cells including macrophages in Pachón cavefish (36).…”

Section: Resultsmentioning

confidence: 99%

Resilience in a Natural Model of Metabolic Dysfunction Through Changes in Longevity and Ageing-Related Metabolites

Medley

Persons

Biswas

et al. 2020

Preprint

View full text Add to dashboard Cite

The Mexican tetra, Astyanax mexicanus, has undergone remarkable physiological and behavioral changes in order to colonize a number of subterranean caves in the Sierra de El Abra region of Mexico. A hallmark of cave-adapted populations is enhanced survival under low-nutrient conditions coupled with hyperglycemia, increased body fat, and insulin resistance, but cavefish appear to avoid the progression of the respective pathologies associated with these conditions and do not exhibit reduced longevity. The metabolic strategies underlying these adaptations are not fully understood. Here, we provide an untargeted metabolomics study of long- and short-term fasting in two A. mexicanus cave populations and one surface population. We find that, although cavefish share many similarities with metabolic syndrome normally associated with the human state of obesity, important differences emerge, including cholesterol esters, urate, intermediates of protein glycation, metabolites associated with hypoxia and longevity, and unexpectedly elevated levels of ascorbate (vitamin C). This work highlights the fact that certain metabolic features associated with human pathologies are not intrinsically harmful in all organisms, and suggests promising avenues for future investigation into the role of certain metabolites in evolutionary adaptation and health. We provide a transparent pipeline for reproducing our analysis and a Shiny app for other researchers to explore and visualize our dataset.

show abstract

Section: Resultsmentioning

confidence: 99%

Resilience in a Natural Model of Metabolic Dysfunction Through Changes in Longevity and Ageing-Related Metabolites

Medley

Persons

Biswas

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies showed that lineage (29) and peritoneal macrophages (30) cultured under high glucose conditions tend to present M2-like phenotype characteristics, which would polarize them toward an adaptive rather than an innate immune response, and other studies relate the impaired phagocytic ability in AM of diabetic rats to reduced phosphorylation of ERK, Akt, and PKC-d resulting from deficient bonding of leukotrienes to FcgR signaling pathways (31). In addition, Ayala et al show that high glucose levels appear to modify macrophage behavior, affecting different aspects of diabetic (impaired phagocytic ability, reduced production of reactive hydrogen species, and reduced expressions of TLR-4 on the cell surface) and healthy bone marrow-derived macrophages under the same LPS stimulus, hypothesizing that hyperglycemia leaves a glucose legacy, altering the basal steady state of macrophages (32). More recently, Tessaro et al (33) also showed that in vitro treatment with insulin is able to amplify inflammatory cytokine secretion by bone marrow-derived macrophages from diabetic mice stimulated with LPS by enhancing phosphorylation of MAPK (p42 MAPK, p44 MAPK, p46 SAPK, p54 SAPK) resulting from TLR-4 activation with LPS, and mice deficient of mechanisms related to detection and phagocytosis, such as expressions of TLR-2 and TLR-4, were observed to be more susceptible to PCM (10).…”

Section: Discussionmentioning

confidence: 99%

Insulin Modulates Inflammatory Cytokine Release in Acute Stages and Augments Expression of Adhesion Molecules and Leukocytes in Lungs on Chronic Stages of Paracoccidioidomycosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

“…The rats (n=48) were randomly divided into four groups (n=12 rats each) ( 36 , 37 ): i) Saline control group; ii) LPS (cat. no.…”

Section: Methodsmentioning

confidence: 99%

Dexmedetomidine alleviates LPS‑induced acute lung injury via regulation of the p38/HO‑1 pathway

et al. 2020

View full text Add to dashboard Cite

Acute lung injury (ALI) is a common critical illness in clinical anesthesia and the intensive care unit that can cause acute hypoxic respiratory insufficiency. Despite various therapeutic regimes having been investigated, there is currently no effective pharmacotherapy available to treat ALI. Previous studies have reported that the NOD-like receptor protein 3 (NLRP3) signaling pathway plays an important role in the inflammatory response and is involved in the pathogenesis of ALI. Moreover, dexmedetomidine (Dex), an α2-adrenergic receptor activating agent, has been routinely used as an adjuvant therapy in treating inflammatory diseases, including ALI. However, the precise pathological mechanisms of Dex in ALI remain to be elucidated. Thus, the present study aimed to investigate the effects of the p38/heme oxygenase 1 (HO-1) signaling pathways in the pathological mechanisms of Dex in ALI. Newborn male Sprague-Dawley rats (n=48) were randomly divided into four groups (n=12 each), and an intravenous injection of lipopolysaccharide (LPS) was used to successfully induce the ALI model, with increased pulmonary damage, cell apoptosis, interleukin-1β (IL-1β) secretion and edema fluid in lungs. Moreover, the mRNA and protein expression levels of NLRP3 were significantly upregulated, while that of HO-1 were downregulated by LPS treatment. Furthermore, the levels of phosphorylated p38 were also upregulated in ALI rats. It was demonstrated that Dex administration significantly alleviated LPS-induced ALI, downregulated the secretion of IL-1β, decreased the expression of NLRP3, inhibited the phospho-activation of p38 and increased HO-1 expression. In addition, pharmacological inhibition of p38 using the inhibitor SB20380 further enhanced the effect of Dex. Collectively, these preliminarily results identified the effects of Dex intervention on the pathogenesis of ALI via the regulation of p38/HO-1 signaling pathways, which impacted the inflammatory effects, thus providing a theoretical basis and novel evidence for the development of new targets for clinical treatment of ALI.

show abstract

High Glucose Environments Interfere with Bone Marrow-Derived Macrophage Inflammatory Mediator Release, the TLR4 Pathway and Glucose Metabolism

Cited by 50 publications

References 76 publications

Resilience in a Natural Model of Metabolic Dysfunction Through Changes in Longevity and Ageing-Related Metabolites

Resilience in a Natural Model of Metabolic Dysfunction Through Changes in Longevity and Ageing-Related Metabolites

Insulin Modulates Inflammatory Cytokine Release in Acute Stages and Augments Expression of Adhesion Molecules and Leukocytes in Lungs on Chronic Stages of Paracoccidioidomycosis

Dexmedetomidine alleviates LPS‑induced acute lung injury via regulation of the p38/HO‑1 pathway

Contact Info

Product

Resources

About