High glucose concentrations induce TNF-α production through the down-regulation of CD33 in primary human monocytes
Open Access
- 14 April 2012
- journal article
- Published by Springer Science and Business Media LLC in BMC Immunology
- Vol. 13 (1), 19
- https://doi.org/10.1186/1471-2172-13-19
Abstract
Background: CD33 is a membrane receptor containing a lectin domain and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) that is able to inhibit cytokine production. CD33 is expressed by monocytes, and reduced expression of CD33 correlates with augmented production of inflammatory cytokines, such as IL-1β, TNF-α, and IL-8. However, the role of CD33 in the inflammation associated with hyperglycemia and diabetes is unknown. Therefore, we studied CD33 expression and inflammatory cytokine secretion in freshly isolated monocytes from patients with type 2 diabetes. To evaluate the effects of hyperglycemia, monocytes from healthy donors were cultured with different glucose concentrations (15-50 mmol/l D-glucose), and CD33 expression and inflammatory cytokine production were assessed. The expression of suppressor of cytokine signaling protein-3 (SOCS-3) and the generation of reactive oxygen species (ROS) were also evaluated to address the cellular mechanisms involved in the down-regulation of CD33. Results: CD33 expression was significantly decreased in monocytes from patients with type 2 diabetes, and higher levels of TNF-α, IL-8 and IL-12p70 were detected in the plasma of patients compared to healthy donors. Under high glucose conditions, CD33 protein and mRNA expression was significantly decreased, whereas spontaneous TNF-α secretion and SOCS-3 mRNA expression were increased in monocytes from healthy donors. Furthermore, the down-regulation of CD33 and increase in TNF-α production were prevented when monocytes were treated with the antioxidant α-tocopherol and cultured under high glucose conditions. Conclusion: Our results suggest that hyperglycemia down-regulates CD33 expression and triggers the spontaneous secretion of TNF-α by peripheral monocytes. This phenomenon involves the generation of ROS and the up-regulation of SOCS-3. These observations support the importance of blood glucose control for maintaining innate immune function and suggest the participation of CD33 in the inflammatory profile associated with type 2 diabetes.Keywords
This publication has 48 references indexed in Scilit:
- Diagnosis and Classification of Diabetes MellitusDiabetes Care, 2011
- Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation?Immunology, 2010
- Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expressionThe American Journal of Clinical Nutrition, 2010
- Differential Effects of Cream, Glucose, and Orange Juice on Inflammation, Endotoxin, and the Expression of Toll-Like Receptor-4 and Suppressor of Cytokine Signaling-3Diabetes Care, 2010
- High Glucose–Induced Oxidative Stress Increases Transient Receptor Potential Channel Expression in Human MonocytesDiabetes, 2010
- Increase in Plasma Endotoxin Concentrations and the Expression of Toll-Like Receptors and Suppressor of Cytokine Signaling-3 in Mononuclear Cells After a High-Fat, High-Carbohydrate MealDiabetes Care, 2009
- Increased secretion of IP-10 from monocytes under hyperglycemia is via the TLR2 and TLR4 pathwayCytokine, 2009
- Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitroCritical Care, 2008
- Evidence of Increased Inflammation and Microcirculatory Abnormalities in Patients With Type 1 Diabetes and Their Role in Microvascular ComplicationsDiabetes, 2007
- High glucose induces IL-1β expression in human monocytes: mechanistic insightsAmerican Journal of Physiology-Endocrinology and Metabolism, 2007