Chong-Jeh Lo1. 1. Department of Surgery, National Cheng Kung University, Tainan, Taiwan. jehlo@mail.ncku.edu.tw
Abstract
BACKGROUND: Patients with diabetes mellitus have increased risk of developing infectious complications following trauma and surgery. Recent studies have attributed altered immunoinflammatory responses of these patients as the cause of the underlying pathophysiology. This study was designed to investigate the effect of hyperglycemia on tissue-fixed macrophages (MO) PGE2 production. METHODS: Experimental hyperglycemia was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin (65 mg/kg). Peritoneal MO were harvested and stimulated with Escherichia coli LPS (1 ng to 1 microg/ml). COX-2 mRNA expression was measured by RT-PCR with specific primers. PGE2 production by peritoneal MO was determined by ELISA. In addition, the effect of hyperglycemia on NFkappaB activation and pro-inflammatory cytokines induced by LPS were studied on RAW 264.7 cells cultured in media with either 5.5 mm or 25 mm of glucose. RESULTS: LPS stimulation induced a dose-dependent response of PGE2 production and COX-2 mRNA expression. MO from diabetic animals produced more COX-2 mRNA and PGE2 than the control animals. LPS stimulation induced NFkappaB activation that was attenuated by hyperglycemia in RAW cells. Similarly, hyperglycemia reduced the production of TNF and IL-6. CONCLUSIONS: Our data suggest that hyperglycemia alters LPS-stimulated macrophage responses by augmenting anti-inflammatory activities such as PGE2. In addition, hyperglycemia also reduces NFkappaB activity and NFkappaB-dependent cytokines production.
BACKGROUND:Patients with diabetes mellitus have increased risk of developing infectious complications following trauma and surgery. Recent studies have attributed altered immunoinflammatory responses of these patients as the cause of the underlying pathophysiology. This study was designed to investigate the effect of hyperglycemia on tissue-fixed macrophages (MO) PGE2 production. METHODS: Experimental hyperglycemia was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin (65 mg/kg). Peritoneal MO were harvested and stimulated with Escherichia coli LPS (1 ng to 1 microg/ml). COX-2 mRNA expression was measured by RT-PCR with specific primers. PGE2 production by peritoneal MO was determined by ELISA. In addition, the effect of hyperglycemia on NFkappaB activation and pro-inflammatory cytokines induced by LPS were studied on RAW 264.7 cells cultured in media with either 5.5 mm or 25 mm of glucose. RESULTS: LPS stimulation induced a dose-dependent response of PGE2 production and COX-2 mRNA expression. MO from diabetic animals produced more COX-2 mRNA and PGE2 than the control animals. LPS stimulation induced NFkappaB activation that was attenuated by hyperglycemia in RAW cells. Similarly, hyperglycemia reduced the production of TNF and IL-6. CONCLUSIONS: Our data suggest that hyperglycemia alters LPS-stimulated macrophage responses by augmenting anti-inflammatory activities such as PGE2. In addition, hyperglycemia also reduces NFkappaB activity and NFkappaB-dependent cytokines production.