Poster presentation. Abstract: It has been shown that the innate immune system plays an important role in the pathogenesis of diabetes. However, the effects of diabetes on the innate immunity have not been well understood. CD14, a receptor for lipopolysaccharide (LPS) and one of the pattern recognition receptors (PRRs), plays an essential role in the innate immune responses. Although clinical studies have shown that CD14 expression in monocytes from diabetic patients is higher than that from nondiabetic individuals, the underlying mechanism has not been defined. In the present study, we determined the effect of elevated concentration of glucose on CD14 expression by U937 mononuclear cells. Real-time PCR showed that high glucose augmented LPS-stimulated CD14 expression by 15-fold as compared with normal glucose. Immunoassay showed a marked enhancement of both membrane-associated and soluble CD14 levels by high glucose. Further investigations revealed that high glucose augmented LPS-stimulated CD14 expression by enhancing NF?B and AP-1 activities. Finally, studies showed that augmentation of LPS-stimulated MMP-1 expression by high glucose was inhibited by anti-CD14 antibodies, suggesting a crucial role of CD14 in high glucose-enhanced
gene expression. Taken together, this study has demonstrated a robust augmentation by high glucose of LPS-stimulated CD14 expression, suggesting that hyperglycemia may enhance the innate immunity.
This study was supported by NIH grant DE16353 and VA Merit Review. Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine; Department of Biostatistics, Bioinformatics & Epidemiology; College of Dental Medicine. Poster design by Lisa M. Fennessy, MUSC Art Services.