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Adhesion between circulating monocytes and vascular endothelial cells is a key initiator of atherosclerosis. In our previous studies, it was demonstrated that the expression of connexin (Cx)43 in monocytes modulates cell adhesion, however, the effects of the expression of Cx43 in endothelial cells remains to be elucidated. Therefore, the present study investigated the role of the expression of Cx43 in endothelial cells in the process of cell adhesion. A total of four different methods with distinct mechanisms were used to change the function and expression of Cx43 channels in human umbilical vein endothelial cells: Cx43 channel inhibitor (oleamide), enhancer (retinoic acid), overexpression of Cx43 by transfection with pcDNA-Cx43 and knock-down of the expression of Cx43 by small interfering RNA against Cx43. The results indicated that the upregulation of the expression of Cx43 enhanced monocyte-endothelial adhesion and this was markedly decreased by downregulation of Cx43. This mechanism was associated with Cx43-induced expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1. The effects of Cx43 in endothelial cells was independent of Cx37 or Cx40. These experiments suggested that local regulation of endothelial Cx43 expression within the vasculature regulates monocyte-endothelial adhesion, a critical event in the development of atherosclerosis and other inflammatory pathologies, with baseline adhesion set by the expression of Cx43. This balance may be crucial in controlling leukocyte involvement in inflammatory cascades. [ABSTRACT FROM AUTHOR]

Preconditioning with sevoflurane (SEV) can protect against ischemia-reperfusion injury in several organs, however, the benefits of SEV against acute lung injury (ALI), induced by intestinal ischemia-reperfusion (IIR), and the underlying mechanisms remain to be elucidated. The present study was designed to investigate the effects of SEV preconditioning on IIR-mediated ALI and the associated mechanisms in a rat model. Female Sprague-Dawley rats treated with 2.3% SEV or apocynin (AP), an inhibitor of NADPH oxidase, were subjected to 75 min superior mesenteric artery occlusion followed by 2 h reperfusion in the presence or absence of the mast cell degranulator compound 48/80 (CP). SEV and AP were observed to downregulate the protein expression levels of p47phox and gp91phox in the lungs of normal rats. IIR resulted in severe lung injury, characterized by significant increases in pathological injury scores, lung wet/dry weight ratio, protein expression levels of p47phox, gp91phox and ICAM-1, the presence of hydrogen peroxide, malondydehyde and interleukin-6, and the activity of myeloperoxidase. In addition, significant reductions were observed in the expression of prosurfactant protein C, accompanied by an increase in MC degranulation, demonstrated by significant elevations in the number of mast cells, expression levels of tryptase and the concentration of β-hexosaminidase. These changes were further augmented in the presence of CP. In addition, SEV and AP preconditioning significantly alleviated the above alterations induced by IIR alone or in combination with CP. These indings suggested that SEV and AP attenuated IIR-induced ALI by inhibiting NADPH oxidase and the synergistic action between oxidative stress and mast cell activation. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical regulator of the cellular-defense response in protection against oxidative injury. Several studies have demonstrated that propofol ameliorates ischemia/reperfusion injury in a number of organs. However, whether propofol exerts renal protection against liver transplantation via Nrf2 activation remains to be elucidated. The aim of the present study was to investigate the effects of orthotopic liver autotransplantation (OLAT) on renal Nrf2 expression and to determine whether propofol protects against kidney injury induced by OLAT via Nrf2 activation. A total of 24 male Sprague Dawley rats were randomly divided into four groups: sham surgery + normal saline (sham group); OLAT + normal saline (OLAT group); OLAT + propofol 50 mg/kg (L-Prop group) and OLAT + propofol 100 mg/kg (H-Prop group). Normal saline and propofol were administered for 3 consecutive days through an intraperitoneal injection prior to surgery. Kidney pathology, blood urea nitrogen (BUN), creatinine (Cr), superoxide anion (O2 •-), hydroxyl radical (.OH), maleic dialdehyde (MDA) and expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1) and NADP quinine oxidoreductase 1 (NQO1) were assessed 8 h after OLAT. It was demonstrated that OLAT induced remote kidney damage. Pretreatment with propofol significantly ameliorated renal pathology and abrogated the increase of the Cr and BUN concentrations, O2 •- and .OH activities, and MDA levels induced by OLAT. In the H-Prop group, Keap1 expression in the cytoplasm was decreased and Nrf2 expression in the nucleus was upregulated, accompanied by an increase of HO-1 and NQO1 expression. The present results suggest that propofol pretreatment exerted renal protection against OLAT, with the upregulation of nuclear Nrf2 expression as a potential mechanism. [ABSTRACT FROM AUTHOR]