The production of reactive oxygen species in TLR-stimulated granulocytes is not enhanced by hyperglycemia in diabetes

Toll-like receptors (TLRs) play an important role in several inflammatory diseases such as diabetes. The present study was to determine whether hyperglycemia in diabetes interferes in reactive oxygen species (ROS) production in granulocytes stimulated with either TLR2/zymosan, TLR4/lipopolysaccharide (LPS) or TLR2,4,9/concanavalin A (ConA). NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and mitogen-activated protein kinase (MAPK) signaling pathways associated with ROS generation in TLR-stimulated granulocytes were evaluated. Our results demonstrate that ROS generation in resting granulocytes derived from patients suffering from Type 2 diabetes mellitus (T2DM) is significantly higher than that observed in equivalent cells from healthy controls. However, ROS formed by TLR-stimulated granulocytes from T2DM patients and healthy subjects were comparable. ROS production by TLR4,9 depends on NADPH-oxidase and MAPK signaling pathways. In contrast, the activation of TLR2 leads to ROS production by a mechanism that is dependent on NADPH oxidase but independent of the MAPK. In conclusion our results suggest that hyperglycemia in diabetes may prime cells metabolically for ROS generation but does not exert any significant effect on TLR-stimulated ROS production and possibly does not aggravate the development of ROS-dependent diabetic complications.