Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we fo...Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP.Moreover,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation.Furthermore,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium.This finding provides a basis for the development of an effective therapeutic approach for treating DP.展开更多
BACKGROUND: Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis. This study aimed to establish a rat model of severe acute pancreatitis (SAP) for investigating monocyte chemotactic ...BACKGROUND: Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis. This study aimed to establish a rat model of severe acute pancreatitis (SAP) for investigating monocyte chemotactic protein-1 (MCP-1) expression in the pathogenesis of the disease. We assessed the effects of the inhibitor of MCP-1, Bindarit, on SAP and explored the mechanisms underlying SAP. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a saline control group (group S), an SAP group (group P), and a Bindarit group (group T). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bilio-pancreatic duct. Based on the SAP model, Bindarit was injected intraperitoneally in group T, and 0.5% methyl cellulose was injected intraperitoneally in groups S and P. In group S, saline was retrogradely infused into the bilpancreatic duct. Serum amylase levels and the histological changes in the pancreas were assessed at different time-points in each group. Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay (ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry, Western blotting, and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Serum amylase levels in groups P and T were higher than those in group S. Serum amylase levels were significantly lower in group T than in group P at 6 and 12 hours after operation. The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were significantly higher than in group S, and significantly lower in group T than in group P at 6 and 12 hours after operation. The pathological damage in the pancreas was milder in group T than in group P. MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S. These expression levels were positively correlated with the pathological damage of pancreatic tissues. The activity of MCP-1 in group T was significantly lower than in group P. CONCLUSION: MCP-1 may play important roles in the pathogenesis of SAP. The data suggest that Bindarit ameliorates SAP by inhibiting the activity of MCP-1 in vivo. (Hepatobiliary Pancreat Dis Int 2010; 9: 201-207)展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81873713,81670984,81873829,and 81700959)the International Cooperation Project of Science and Technology in Guangdong Province(Grant No.2016B050502008).
文摘Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP.Moreover,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation.Furthermore,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium.This finding provides a basis for the development of an effective therapeutic approach for treating DP.
基金supported by grants from the social Burteall Foundation of Nantong(S5054)
文摘BACKGROUND: Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis. This study aimed to establish a rat model of severe acute pancreatitis (SAP) for investigating monocyte chemotactic protein-1 (MCP-1) expression in the pathogenesis of the disease. We assessed the effects of the inhibitor of MCP-1, Bindarit, on SAP and explored the mechanisms underlying SAP. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a saline control group (group S), an SAP group (group P), and a Bindarit group (group T). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bilio-pancreatic duct. Based on the SAP model, Bindarit was injected intraperitoneally in group T, and 0.5% methyl cellulose was injected intraperitoneally in groups S and P. In group S, saline was retrogradely infused into the bilpancreatic duct. Serum amylase levels and the histological changes in the pancreas were assessed at different time-points in each group. Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay (ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry, Western blotting, and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Serum amylase levels in groups P and T were higher than those in group S. Serum amylase levels were significantly lower in group T than in group P at 6 and 12 hours after operation. The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were significantly higher than in group S, and significantly lower in group T than in group P at 6 and 12 hours after operation. The pathological damage in the pancreas was milder in group T than in group P. MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S. These expression levels were positively correlated with the pathological damage of pancreatic tissues. The activity of MCP-1 in group T was significantly lower than in group P. CONCLUSION: MCP-1 may play important roles in the pathogenesis of SAP. The data suggest that Bindarit ameliorates SAP by inhibiting the activity of MCP-1 in vivo. (Hepatobiliary Pancreat Dis Int 2010; 9: 201-207)
