Chronic hyperglycemia and inflammation -
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Jennifer Chesak. Dominic D'Agostino, PhD. Inflammation and glucose levels: How high blood sugar can turn a good system bad. Written By Esti Schabelman, MD. Article highlights Inflammation is a natural defense system in which your body attacks something it sees as a harm, such as a cut, an infection or even stress.
That response produces symptoms like redness, pain, swelling, warmth, and loss of function. Chronic inflammation can increase your risk of heart attack, obesity, cancer and diabetes, among other conditions.
High blood sugar, or hyperglycemia, and the insulin resistance that often accompanies it, can be proinflammatory. A healthy diet and lifestyle can greatly reduce your chance of chronic inflammation.
The gene expression was around four times the basal level but was not significantly different whether the cells were cultivated in hypoxia or in hyperglycemia Fig 3A.
As a result, the combination of hypoxia and hyperglycemia has a synergistic effect for long term TNF-α gene expression. A TNF-α, B IL-1a, C IL-6, D CSF2, GM-CSF.
Unlike TNF-α, the LPS activation did not increase the IL-1 gene expression after one hour when cells were cultivated in normoxia.
In sharp contrast, hypoxia had a huge effect as the IL-1a gene expression was circa five fold higher for cells cultivated in hyperglycemia and normoglycemia.
After 17 hours, the IL-1a expression decreased to its basal level in normoglycemia whereas that measured in hyperglycemic conditions remained high Fig 3B. After 17 hours post-activation, hyperglycemia and hypoxia are required to maintain a high expression of IL-1A.
The addition of lipopolysaccharide to macrophages triggered a slight increase of IL-6 gene expression irrespective of the culture condition Fig 3C. When hypoxia was combined with hyperglycemic conditions, IL-6 gene expression increased dramatically for this group after 17 hours post activation.
Interestingly, cells cultivated in normoxia and hyperglycemia exhibited an increased expression of IL-6 after 17 hours compared to that after 1 hour Fig 3C. In this case, hyperglycemia has an effect on its own but it was amplified by hypoxia. Macrophage activation did not have any effect on GM-CSF gene expression of each group one hour after LPS addition Fig 3D.
A long term effect of hypoxia was observed as the gene expression of cells cultivated in hypoxia was half that of those cultivated in normoxia. Therefore, hyperglycemia and hypoxia have a negative effect on inflammation as they upregulate the gene expression of the inflammatory cytokines TNF-α, IL-6 and IL-1 in activated macrophages.
The LPS activation of macrophages led to a slight increase of the CD gene expression in normoxia and normoglycemia Fig 4A.
Hypoxia and hyperglycemia had a long term effect on this gene expression. Low oxygen tension and high glucose concentration negatively impacted the CD expression on their own.
Macrophages exhibited a drastic upregulation of the Class B Scavenger receptor gene when the cells were cultivated in hypoxia. No effect was observed in normal O 2 condition Fig 4B.
After 17 hours post-activation, Class B Scavenger gene expression recovered its basal level irrespective of the culture conditions. However hypoxia had a slight positive effect when cells were cultured in hyperglycemia. Hence, hypoxia and hyperglycemia decreases the abilities of activated macrophages for phagocytosis because the expression of CD and Class B scavenger are downregulated.
The TGF-β1 gene expression was not modified one hour after activation of macrophages regardless of the O 2 and glucose conditions Fig 5. This expression did not change after 17 hours post activation either. Hence a low O 2 tension and hyperglycemic conditions does not have any impact on TGF-β production Fig 5.
SOCS-3 was upregulated one hour after LPS activation when the cells were cultivated in hypoxia. This upregulation was higher for macrophages cultivated in normoglycemia Fig 6. The SOC-3 gene expression decreased to its basal level after 17 hours in these groups. In contrast, the cells cultivated in normoxia and hyperglycemia exhibited an upregulation of SOCS The goal of this study was to analyze the impact of hyperglycemia on the macrophage phenotype focusing on proteins involved in inflammation, proliferation, apoptosis, ECM breakdown and wound healing.
For this purpose, a gene expression microarray analysis was performed on activated macrophages cultured in a hyperglycemic and hypoxic environment with a low quantity of bovine serum with the aim of mimicking the chronic wound milieu.
Subsequently, the effect of hyperglycemia and hypoxia were analyzed separately to understand their contribution in the chronic wounds. Lastly a potential synergistic effect of high glucose concentration and low O 2 tension was evaluated.
Hyperglycemia has several detrimental effects on human homeostasis. A chronic high glucose concentration leads to a process of protein glycation and the production of advanced glycation endproducts AGEs. AGEs promote macrophage activation via NF- κ B and stimulate the production of reactive oxygen species ROS [ 22 ].
As a consequence, diabetes predisposes to epigenetic changes which lead to chronic inflammation [ 23 ]. The microarray results show that 13 pro-inflammatory cytokines and 10 chemokines were upregulated in hyperglycemia, thereby confirming the perpetual dysregulation of the inflammatory homeostasis.
Pro-inflammatory macrophages are more metabolically active in hyperglycemic conditions and exclusively use glucose as a source of energy [ 24 ]. Hence, this mode of energy production can contribute to the failure to resolve inflammation. Chronic wounds are characterized by the recruitment and the persistence of immune cells in the wound bed neutrophils and macrophages [ 25 ].
The results showed the upregulation of 11 anti-apoptotic genes and the downregulation of 3 pro-apoptotic genes, indicating the direct impact of hyperglycemia on the large number of macrophages inside the cutaneous wound bed.
One major feature of impaired wound healing is the massive breakdown of extracellular matrix. High glucose concentration triggers the production and secretion of metalloproteinases such as MMP-9 and MMP-2 by fibroblasts, keratinocytes and macrophages [ 25 , 26 ].
In our conditions, hyperglycemia did not have a direct effect on proteases as only MMP-7 was affected. In addition, this enzyme was slightly downregulated. Lipopolysacharide LPS is an outer membrane component of Gram negative bacteria which activates macrophages [ 27 ]. LPS contact with TLR receptors orientates macrophages towards a pro-inflammatory M1 phenotype.
This phenotype is characterized by the production of inflammatory cytokines such as IL-6, IL-1, TNF-α, reactive species of oxygen ROS and NO [ 28 ]. The expression of inflammatory cytokines is based on the NF- κ B activation in macrophages [ 29 ].
AGEs interacting with RAGE, their membrane receptor, can be a continuous activator of NF- κ B. As a result, AGEs increase the production of pro-inflammatory cytokines as previously described [ 30 ].
Hypoxia is associated with the activation of hypoxia inducible factors HIFs which is the key mediator of the induction of IL-6, IL-1, TNF-α [ 31 ]. Hence, hypoxia and hyperglycemia could have a synergistic effect on the production of pro-inflammatory cytokines.
In addition, a cross-talk exists between HIF and NF- κ B to increase this production. We analyzed in detail the impact of hypoxia and high glucose on cytokine production with a kinetic view. After one hour post LPS activation, the combination of hypoxia and hyperglycemia had a dramatic effect on the expression of TNF-α and IL The combination of hyperglycemia and hypoxia is required to induce a sustained production of pro-inflammatory cytokines as the same phenomenon was observed for TNF-α and IL Beside its major role in inflammation, it has been recently shown that IL-6 could have anti-inflammatory effects via modulation of macrophage phenotype [ 32 ].
IL-6 promote the M2 phenotype of macrophages by inducing the expression of the IL-4 receptor [ 32 ]. In this study, the IL-4 receptor was not upregulated.
Several studies have reported on the anti-inflammatory effect of IL-6 and the dependency on the concentration. In this study, Il-6 was dramatically upregulated and orientated its action towards chronic inflammation [ 32 ].
Regarding IL-1, only hypoxia had a short term impact on the expression of this cytokine. An effect was observable 17 hours post activation for the cells cultivated in hypoxia and hyperglycemia.
This shows their importance for a long term effect on inflammation. Moreover, the sustained and prolonged production of IL-1 contributes to diminish wound healing by activating TLR receptors and maintaining macrophages in a M1 phenotype [ 33 ].
Granulocyte macrophage colony-stimulating factor GM-CSF is highly upregulated in hyperglycemic conditions. GM-CSF is produced during the inflammation phase and is a marker of M1 macrophages [ 34 ]. This cytokine stimulates the production of chemokines such as CCL2 and CCL3 and is involved in the recruitment of myeloid cells within the wound [ 33 ].
The GM-CSF expression is induced by pro-inflammatory cytokines such as IL-1 and TNF-alpha. As a consequence, the high production of pro-inflammatory cytokines by high glucose and low O2 tension increases the expression of GM-CSF, which has also a negative effect on inflammation.
In our conditions, GM-CSF was not impacted by hyperglycemia which is not consistent with the results of the micro array.
Suppressor of cytokine signaling 3 SOCS3 is associated with the pro-inflammatory M1 phenotype of macrophages. In addition, SOCS3 decreases the phagocytic activities of macrophages for apoptotic neutrophils.
The decrease of clearance of dead neutrophils impedes the resolution of inflammation and a pro-inflammatory environment shows a strong upregulation of SOCS3 [ 35 , 36 ]. Hyperglycemia seems to have a short term negative effect on SOCS3.
Surprisingly, hyperglycemia seems to favour the resolution of inflammation at this time point. However, hyperglycemia has a negative effect after 17 hours when the cells are cultivated in hyperglycemia. As SOCS-3 is upregulated in this study, this confirms the inflammatory effect of IL-6 in hyperglycemia.
It has been shown this cytokine has an anti-inflammatory effect only when SOCS-3 was downregulated or ablated [ 37 ]. Hyperglycemia combined with hypoxia also led to the upregulation of a panel of chemokines. Among them, CCL-4 is of great interest because it activates neutrophils which can trigger neutrophilic inflammation [ 38 , 39 ].
In addition, this chemokine triggers the production of pro-inflammatory cytokines. Five C-X-C chemokines CXCL 1- CXCL5 were also upregulated in hyperglycemia.
For example, CXCL2 is highly expressed. Moreover, CXCL2 recruit neutrophils to infection sites. Overall, the other chemokines have the same effect, recruiting leucocytes in the wound. Hence, hyperglycemia and hypoxia create a vicious circle which maintains a high inflammation in the wound and prevents the switch from the inflammatory phase to the proliferative one.
Phagocytosis of dead cells is required for the resolution of inflammation and the transition towards the proliferative phase [ 41 ] because impaired cell clearance has been observed in diabetic wounds [ 42 ]. CD36 is a member of the class B scavenger receptor family found in macrophages.
CD36 is an efferocytosis receptor which acts in combination with α v β 3 integrin to engulf dead neutrophils [ 41 ]. Unlike the normoglycemic conditions, CD36 expression does not increase in hyperglycemia one hour after LPS activation.
This result shows the impaired phagocytic activities of macrophages cultivated in high glucose. In addition, CD36 mediate s the bacteria phagocytosis and the production of inflammatory molecules such as IL-8 [ 43 ].
Hence, the absence of an upregulation of CD36 following the activation by LPS suggests the lower ability of macrophages to combat infection when they are in a hyperglycemic milieu. Class B scavenger type I receptors CLA-1 are also involved in the pathogen s recognition and the removal of apoptotic cells.
They have a lot of structural similarities with CD36 [ 43 ]. They also have an effect on cytokine production as Knock Out CLA-1 mice expressed more inflammatory cytokines than the wild type [ 43 ].
The results showed that hypoxia is an important stimulus for Class B scavenger expression because its expression is multiplied by 12 in hypoxia over that in the normoxic conditions.
Hyperglycemia negatively modulates this upregulation showing once again the impaired phagocytic abilities of diabetic macrophages, thereby settling down the chronic inflammation in the cutaneous wound.
TGF-B1 is a master regulator of the wound healing process by promoting the switch between the inflammation and the proliferative phase [ 44 ]. The TGF-B activity counterbalances the effect of TNF-alpha in macrophages [ 45 ] and favours angiogenesis, ECM deposition and fibroblast proliferation.
Hyperglycemia and hypoxia did not have any effect on its gene expression. Hence, hyperglycemia only negatively impacts the expression of pro-inflammatory cytokines but not those involved in wound healing.
Hyperglycemia has a negative impact on the wound healing of foot diabetic ulcers. High glucose level acts in synergy with hypoxia to maintain the state of chronic inflammation observed in chronic wounds.
Hyperglycemia increases the expression of pro-inflammatory cytokines and chemokines by macrophages and decreases their ability of phagocytosis, required for the resolution of inflammation. By contrast, the cytokines involved in wound healing were not impacted by the high glucose concentration.
This overview of the macrophage behavior cultivated in hyperglycemia and hypoxia could be helpful towards discovering novel relevant targets for the treatment of foot diabetic ulcers. The authors would like to thank Dr Oliver Carroll for his technical guidance in the project, Dana Toncu for editorial and critical assessment of the manuscript, and Mr Anthony Sloan for his editorial assistance in finalizing the manuscript.
Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Diabetic foot ulcers DFUs are characterized by a chronic inflammation state which prevents cutaneous wound healing, and DFUs eventually lead to infection and leg amputation.
Introduction Diabetic foot ulcers are the most common, painful and crippling complications of diabetes mellitus [ 1 ]. In pathological conditions, macrophages are locked in the M1 phenotype, thereby leading to chronic inflammation Hypoxia in DFU creates conditions that are disadvantageous because the low oxygen tension induces the increased release of pro-inflammatory cytokines via the activation of NF- κ B signaling pathways [ 10 , 11 ].
Download: PPT. Fig 1. Differentiation and activation of macrophages cultivated in hyperglycemia and hypoxia. Schreyer, S. Obesity and diabetes in TNF-α receptor- deficient mice. Bernstein, L. Effects of etanercept in patients with the metabolic syndrome.
Dominguez, H. Metabolic and vascular effects of tumor necrosis factor-α blockade with etanercept in obese patients with type 2 diabetes. Lo, J. Effects of TNF-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome. Ofei, F. Effects of an engineered human anti-TNF-α antibody CDP on insulin sensitivity and glycemic control in patients with NIDDM.
Diabetes 45 , — Paquot, N. No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.
CAS PubMed Google Scholar. Rosenvinge, A. Insulin resistance in patients with rheumatoid arthritis: effect of anti-TNFα therapy. Kiortsis, D. Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis.
Stanley, T. TNF-α antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. Yazdani-Biuki, B. Relapse of diabetes after interruption of chronic administration of anti-tumor necrosis factor-α antibody infliximab: a case observation.
Diabetes Care 29 , — Improvement of insulin sensitivity in insulin resistant subjects during prolonged treatment with the anti-TNF-α antibody infliximab. Weisberg, S. Obesity is associated with macrophage accumulation in adipose tissue. Xu, H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
References 41 and 42 identified macrophages in adipose tissue and showed that their numbers increased with obesity. Lumeng, C. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56 , 16—23 Shaul, M. Kosteli, A.
Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. Herrero, L. Inflammation and adipose tissue macrophages in lipodystrophic mice. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. Liu, J.
Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nature Med. Wu, H. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity.
Circulation , — Feuerer, M. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Ilan, Y. Baecher-Allan, C. Human regulatory T cells and their role in autoimmune disease.
Roncarolo, M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Maedler, K. Leptin modulates β cell expression of IL-1 receptor antagonist and release of IL-1β in human islets. Glucose-induced β-cell production of interleukin-1β contributes to glucotoxicity in human pancreatic islets.
The first description of the role of IL-1β in T2D. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56 , — The original description of macrophage infiltration in islets of patients with T2D.
Carmeliet, P. Angiogenesis in life, disease and medicine. Nature , — Hosogai, N. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation.
Yin, J. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Pasarica, M. Reduced oxygenation in human obese adipose tissue is associated with impaired insulin suppression of lipolysis. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response.
Diabetes 58 , — Murdoch, C. Hypoxia regulates macrophage functions in inflammation. Burke, B. Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy.
Cinti, S. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. Lipid Res. Strissel, K. Adipocyte death, adipose tissue remodeling, and obesity complications.
Arkan, M. IKK-β links inflammation to obesity-induced insulin resistance. Cai, D. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Solinas, G. JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction. FASEB J. Shi, H. TLR4 links innate immunity and fatty acid-induced insulin resistance.
Sabio, G. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity.
Tuncman, G. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Cell , — Zhang, X. Cell , 61—73 Eldor, R. Conditional and specific NF-κB blockade protects pancreatic β cells from diabetogenic agents.
Mooney, R. Counterpoint: interleukin-6 does not have a beneficial role in insulin sensitivity and glucose homeostasis. Pedersen, B. Point: interleukin-6 does have a beneficial role in insulin sensitivity and glucose homeostasis. Fried, S. Omental and subcutaneous adipose tissues of obese subjects release interleukin depot difference and regulation by glucocorticoid.
Wunderlich, F. Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action.
Matthews, V. Interleukindeficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 53 , — Hyperglycemia-induced β-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes.
Diabetes 48 , — Glucose induces β-cell apoptosis via upregulation of the Fas-receptor in human islets. Diabetes 50 , — Schumann, D. The Fas pathway is involved in pancreatic β cell secretory function. Boni-Schnetzler, M. Increased interleukin IL -1β messenger ribonucleic acid expression in β-cells of individuals with type 2 diabetes and regulation of IL-1β in human islets by glucose and autostimulation.
Article PubMed PubMed Central CAS Google Scholar. Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I.
Endocrinology , — Toll-like receptor 2-deficient mice are protected from insulin resistance and β cell dysfunction induced by a high-fat diet. Haversen, L. Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages.
Atherosclerosis , — Lee, J. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4.
Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. Zhou, R. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. A study that describes the mechanism of glucose-induced IL-1β production in pancreatic islets.
van de Veerdonk, F. Reactive oxygen species-independent activation of the IL-1β inflammasome in cells from patients with chronic granulomatous disease.
Meissner, F. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood , — Schroder, K. The NLRP3 inflammasome: a sensor for metabolic danger? Biologic basis for interleukin-1 in disease.
Blood 87 , — Bruun, J. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue AT : implication of macrophages resident in the AT. Harman-Boehm, I.
Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. Kanda, H. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.
Sartipy, P. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Kamei, N. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. Jiao, P.
Obesity-related upregulation of monocyte chemotactic factors in adipocytes: involvement of nuclear factor-κB and c-Jun NH2-terminal kinase pathways.
IL-1β-MyD88 signaling is central to islet chemokine secretion in response to metabolic stress: evidence from a spontaneous model of type 2 diabetes, the GK rat. Diabetologia 50 S Marselli, L. Evidence of inflammatory markers in β cells of type 2 diabetic subjects.
Diabetologia 50 , S—S Wolf, A. Adiponectin induces the anti-inflammatory cytokines IL and IL-1RA in human leukocytes. Greenstein, A. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients.
Rutkowski, J. Mechanisms of obesity and related pathologies: the macro- and microcirculation of adipose tissue. FEBS J. Fleischman, A. Salsalate improves glycemia and inflammatory parameters in obese young adults.
Diabetes Care 31 , — Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Gonzalez-Gay, M. Anti-tumor necrosis factor-α blockade improves insulin resistance in patients with rheumatoid arthritis.
Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-α therapy. NY Acad. Huvers, F. Improved insulin sensitivity by anti-TNFα antibody treatment in patients with rheumatic diseases.
Yuan, M. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ. This study initially identified a potential role for NF-κB in T2D and showed that salicylates improved blood glucose levels in rodent models. Frantz, B. The effect of sodium salicylate and aspirin on NF-κB.
Jurivich, D. Effect of sodium salicylate on the human heat shock response. Hundal, R. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes.
Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. Leahy, J. Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions.
Yki-Jarvinen, H. Hyperglycemia decreases glucose uptake in type I diabetes. Diabetes 36 , —
For oxidative stress and Alzheimers disease information about PLOS Subject Areas, click here. Diabetic foot Chronuc DFUs hyperglyxemia characterized Coconut Oil for Cooking a Dietary choices for prevention inflammation state which prevents cutaneous wound healing, and DFUs eventually lead to infection and leg amputation. Macrophages located in DFUs are locked in an pro-inflammatory phenotype. In this study, the effect of hyperglycemia and hypoxia on the macrophage phenotype was analyzed. For this purpose, a microarray was performed to study the gene expression profile of macrophages cultivated in a high glucose concentration.
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