Effect of milrinone on the inflammatory response and NF-kB activation in renal ischemia-reperfusion injury in mice / 대한마취과학회지

BACKGROUND: Milrinone increases intracellular adenosine 3',5'-cyclic monophosphate concentration and enhances vascular relaxation. Nuclear factor-kappa B (NF-kB) plays a key role in inflammatory responses during ischemia-reperfusion (I/R) injury. We aimed to investigate the effect of milrinone on the inflammatory responses and NF-kB activation in renal I/R injury in mice. METHODS: Thirty C57BL/6 mice were allocated into 3 groups. In group S (n = 10), only right nephrectomy was done. In group C (n = 10), the left kidney was subjected to 30 min of ischemia after right nephrectomy. In group M (n = 10), milrinone (5 microg/kg) was administered before ischemia. After 24 hours of reperfusion, the serum creatinine was measured, kidney samples were obtained for histology, and expressions of NF-kB and proinflammatory cytokines were analyzed. RESULTS: In group C, the serum creatinine concentration was markedly elevated, compared with group S. Creatinine concentration in group M was also elevated, but it was significantly lower than that in group C. Histologic evidence of renal damage was severe in group C, but it was improved in group M. In groups C and M, expression of NF-kB, tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) mRNA increased significantly compared with group S (P < 0.05). But group M showed a lower expression of NF-kB, TNF-alpha, ICAM-1, MCP-1 and MIP-2 mRNA than group C (P < 0.05). CONCLUSIONS: Milrinone treatment attenuates the renal inflammatory response and activation of NF-kB, resulting in improvement of renal function and tissue injury.

Helicobacter pylori Infection Enhances Gastric Mucosal Inflammation in Individuals Carrying the 260-T Allele of the CD14 Gene

BACKGROUND/AIMS: We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population. METHODS: The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA. RESULTS: CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection. CONCLUSIONS: In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.