Regulation of LPS stimulated ROS production in peritoneal macrophages from alloxan-induced diabetic rats: Involvement of high glucose and PPARγ

Abstract

An increased occurrence of long term bacterial infections is common in diabetic patients. Bacterial cell wall components are described as the main antigenic agents from these microorganisms and high blood glucose levels are suggested to be involved in altered immune response. Hyperglycemia is reported to alter macrophages response to lipopolysaccharide (LPS) and peroxisome proliferators activated receptor gamma (PPARγ) expression. Additionally, glucose is the main metabolic fuel for reduced nicotinamide adenine dinucleotide phosphate (NADPH) production by pentose phosphate shunt. In this work, lipopolysaccharide (LPS) stimulated reactive oxygen species (ROS) and nitrite production were evaluated in peritoneal macrophages from alloxan-induced diabetic rats. Cytosolic dehydrogenases and PPARγ expression were also investigated. LPS was ineffective to stimulate ROS and nitrite production in peritoneal macrophages from diabetic rats, which presented increased glucose-6-phosphate dehydrogenase and malate dehydrogenase activity. In RAW 264.7 macrophages, acute high glucose treatment abolished LPS stimulated ROS production, with no effect on nitrite and dehydrogenase activities. Peritoneal macrophages from alloxan-treated rats presented reduced PPARγ expression. Treating RAW 264.7 macrophages with a PPARγ antagonist resulted in defective ROS production in response to LPS, however, stimulated nitrite production was unaltered. In conclusion, in the present study we have reported reduced nitric oxide and reactive oxygen species production in LPS-treated peritoneal macrophages from alloxan-induced diabetic rats. The reduced production of reactive oxygen species seems to be dependent on elevated glucose levels and reduced PPARγ expression.