“…Acute hyperglycaemia significantly altered innate immune responses to infection, causing poor outcomes in hospitalised hyperglycaemic patients [53]. High glucose concentrations alone may alter the production of immune mediators in RAW264.7 cells [54]. Although control of the serum sugar level is an effective treatment strategy for infections in patients with diabetes, measures to prevent immune modulation induced by toxic AGEs have not been fully considered.…”
Hyperglycaemia provides a suitable environment for infections and the mechanisms of glucose toxicity include the formation of advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups. Among AGE-associated phenotypes, glycolaldehyde-derived toxic AGE (AGE-3) is involved in the pathogenesis of diabetic complications. Internalisation of endotoxin by various cell types contributes to innate immune responses against bacterial infection. An endotoxin derived from Gram-negative bacteria, lipopolysaccharide (LPS), was reported to enhance its own uptake by RAW264.7 mouse macrophage-like cells, and an LPS binding protein, CD14, was involved in the LPS uptake. The LPS uptake induced the activation of RAW264.7 leading to the production of chemokine CXC motif ligand (CXCL) 10, which promotes T helper cell type 1 responses. Previously, we reported that AGE-3 was internalised into RAW264.7 cells through scavenger receptor-1 Class A. We hypothesized that AGEs uptake interrupt LPS uptake and impair innate immune response to LPS in RAW264.7 cells. In the present study, we found that AGE-3 attenuated CD14 expression, LPS uptake, and CXCL10 production, which was concentration-dependent, whereas LPS did not affect AGE uptake. AGEs were reported to stimulate the receptor for AGEs and Toll-like receptor 4, which cause inflammatory reactions. We found that inhibitors for RAGE, but not Toll-like receptor 4, restored the AGE-induced suppression of CD14 expression, LPS uptake, and CXCL10 production. These results indicate that the receptor for the AGE-initiated pathway partially impairs the immune response in diabetes patients.
“…Acute hyperglycaemia significantly altered innate immune responses to infection, causing poor outcomes in hospitalised hyperglycaemic patients [53]. High glucose concentrations alone may alter the production of immune mediators in RAW264.7 cells [54]. Although control of the serum sugar level is an effective treatment strategy for infections in patients with diabetes, measures to prevent immune modulation induced by toxic AGEs have not been fully considered.…”
Hyperglycaemia provides a suitable environment for infections and the mechanisms of glucose toxicity include the formation of advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups. Among AGE-associated phenotypes, glycolaldehyde-derived toxic AGE (AGE-3) is involved in the pathogenesis of diabetic complications. Internalisation of endotoxin by various cell types contributes to innate immune responses against bacterial infection. An endotoxin derived from Gram-negative bacteria, lipopolysaccharide (LPS), was reported to enhance its own uptake by RAW264.7 mouse macrophage-like cells, and an LPS binding protein, CD14, was involved in the LPS uptake. The LPS uptake induced the activation of RAW264.7 leading to the production of chemokine CXC motif ligand (CXCL) 10, which promotes T helper cell type 1 responses. Previously, we reported that AGE-3 was internalised into RAW264.7 cells through scavenger receptor-1 Class A. We hypothesized that AGEs uptake interrupt LPS uptake and impair innate immune response to LPS in RAW264.7 cells. In the present study, we found that AGE-3 attenuated CD14 expression, LPS uptake, and CXCL10 production, which was concentration-dependent, whereas LPS did not affect AGE uptake. AGEs were reported to stimulate the receptor for AGEs and Toll-like receptor 4, which cause inflammatory reactions. We found that inhibitors for RAGE, but not Toll-like receptor 4, restored the AGE-induced suppression of CD14 expression, LPS uptake, and CXCL10 production. These results indicate that the receptor for the AGE-initiated pathway partially impairs the immune response in diabetes patients.
“…Mirhafez et al found that individuals with metabolic syndrome (MetS) had higher serum IL-1α levels than healthy controls [ 34 ]. On the contrary, Cantuaria et al found that the IL-1α levels decreased after high glucose and lipopolysaccharide (LPS) stimulation [ 35 ]. The use of an in vitro cell line may be the root cause of this contradiction.…”
Hyperglycemia associated with prediabetes (PD) alters NLRP3 inflammasome activity and related interleukins, yet no study has evaluated the expression of the NLRP3 inflammasome complex and related interleukins in individuals with a PD condition that did or did not develop type 2 diabetes mellitus (T2DM). This study investigated the effect of 6 months of lifestyle modification on the expression of the NLRP3 inflammasome and related interleukins (1α, 1β, 18, 33 and 37) in the sera of individuals with a PD condition that did or did not develop T2DM. This interventional study included 67 Saudi adults (mean age = 41.9 ± 8.0 years, mean BMI = 33.2 ± 5.5 kg/m2). Overnight-fasting serum samples were collected at baseline and at the 6-month follow-up. Serum levels of NLRP3, capsase-1 and related ILs were analyzed at both visits using commercially available immunoassay kits. Results showed that IL-1α increased in the PD group that developed T2DM (p = 0.046), IL-33 decreased in the PD group that reverted to normal (p < 0.001) and NLRP3 decreased in the PD group that remained PD (p = 0.01). Results also showed a positive over-time correlation between NLRP3 and both IL-1α and IL-33 (p < 0.001 and p = 0.028, respectively). In conclusion, glycemic control favorably altered NLRP3 inflammasome complex activity, and lifestyle modification in PD individuals is crucial in reversing harmful metabolic and inflammatory phenotypes.
“…The intervention of CAo after 29 days in the CAo + CAt group had already induced the increase in SOD antioxidant capacity to be more responsive compared to the other 2 groups. Pieme et al [ 28 ] found that uncomplicated DM and complicated DM patients have significantly more antioxidants compared to non-DM patients. This study also found that the pro-oxidants, which are MDA and nitrite oxide (NO), were significantly higher in DM patients compared to non-DM patients.…”
Introduction. Uncontrolled diabetes mellitus (DM) is related to skin disorders, particularly dry skin. Pathogenesis of dry skin in type 2 diabetes mellitus (T2DM) rises from the chronic hyperglycemia causing an increase in advanced glycation end-products (AGEs), proinflammatory cytokines, and oxidative stress. Combination of oral and topical Centella asiatica (CA) is expected to treat dry skin in T2DM patients more effectively through decreasing N(6)-carboxymethyl-lysine (CML) and interleukin-1α (IL-1α) and increasing superoxide dismutase (SOD) activity. Methods. A three-arm prospective, double-blind, randomized, controlled study was performed to evaluate the efficacy of the oral and topical CA extract in 159 T2DM patients with dry skin. The subjects were divided into the CA oral (CAo) 2 × 1.100 mg + CA topical (CAt) 1% ointment group, oral placebo (Plo) + CAt group, and Plo and topical placebo (Plt) group. Dry skin assessment was performed on day 1, 15, and 29, while evaluation of CML, IL-1α, and SOD activity was on day 1 and 29. Result. Effectivity of CAo + CAt combination was assessed based on HbA1c and random blood glucose (RBG). In well-controlled blood glucose, on day 29, the percentage of SRRC decrement was greater in the CAo + CAt group compared to the control group (p=0.04). SCap value in the CAo + CAt group was greater than that in the control group (p=0.01). In the partially controlled blood glucose, increment of SOD activity in the CAo + CAt group was greater than that in the control group (p=0.01). There were medium-to-strong correlation between CML with SOD (r = 0.58, p<0.05) and IL-1α with SOD (r = 0.70, p<0.05) in well-controlled blood glucose. Systemic and topical adverse events were not significantly different between groups. Conclusion. CAo and CAt combination can be used to significantly improve dry skin condition through increasing SOD activity in T2DM patients with controlled blood glucose.
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