Beraprost enhances the APC function of B cells by upregulating CD86 expression levels.

Lipid mediators are emerging as important regulators of the immune system. Based on our previous result that shows strong expression of prostacyclin synthase in the germinal center, we investigated whether prostacyclin would regulate the APC function of B cells. Owing to the very short half-life of prostacyclin in experimental conditions, we used a more stable analog, beraprost.

Rapid determination of blood coagulation factor XIII activity using protein arrays for serodiagnosis of human plasma.

We developed a novel on-chip assay using protein arrays for quantitative and rapid analysis of blood coagulation factor XIII (FXIII) activity in human plasma. FXIII is activated by concerted action of thrombin and Ca(2+) and plays essential roles in hemostasis, angiogenesis, and wound healing. We fabricated protein arrays by immobilizing fibrinogen onto the 3-aminopropyltrimethoxysilane layer of well-type arrays and determined FXIII activity by analyzing biotinylated fibrinogen with Cy3-conjugated streptavidin.

IL-4 and IL-13 suppress prostaglandins production in human follicular dendritic cells by repressing COX-2 and mPGES-1 expression through JAK1 and STAT6.

Originally discovered as a B cell growth and differentiation factor, IL-4 displays a variety of functions in many different cell types. Germinal center T cells are abundant producers of IL-4. In a recent report, we demonstrated that IL-4 inhibits prostaglandins (PGs) production in follicular dendritic cell (FDC)-like cells, HK.

Leptin's neuroprotective action in experimental transient ischemic damage of the gerbil hippocampus is linked to altered leptin receptor immunoreactivity.

Circulating leptin crosses blood-brain barrier to provide control of feeding behavior and energy balance. We investigated changes in leptin and leptin receptor (ObR) in the gerbil hippocampal CA1 region (CA1) after transient cerebral ischemia, and examined effects of leptin on ischemic damage. In vehicle-treated ischemia (vehicle-ischemia) group, the number of survived neurons in the CA1 was 16.

Antioxidant enzymes are differently changed in experimental ischemic hippocampal CA1 region following repeated restraint stress.

Restraint stress induces physiological changes in the brain. In the present study, we observed the effects of repeated stress on ischemic damage associated with oxidative stress in gerbils. Animals were placed into restrainers for 5h (between 09:30 h and 14:30 h) for 21 consecutive days prior to 5 min of transient cerebral ischemia.

Changes in corticosteroid hormone receptors in the ischemic gerbil hippocampal CA1 region following repeated restraint stress.

Restraint stress produces physiological changes including suppression of long-term potentiation in the brain. We observed the effects of repeated stress on ischemic damage associated with corticosteroid hormone receptors in gerbils. Animals were placed into restrainers for 5 h (between 09:30 h and 14:30 h) for 21 consecutive days prior to induction of transient cerebral ischemia.

Cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells.

We investigated cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells. Cells were loaded with 0.5-10 μg/mL DH-II-24 for 12 h, and intracellular reactive oxygen species (ROS) and intracellular Ca(2+) levels, in situ tissue transglutaminase (tTGase) activity, cell viability, cell morphology and cell cycle were examined.

Comparison of phosphorylated extracellular signal-regulated kinase 1/2 immunoreactivity in the hippocampal Ca1 region induced by transient cerebral ischemia between adult and aged gerbils.

In this study, the authors examined the difference of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in the hippocampal CA1 region (CA1) between adult and aged gerbils after 5 min of transient cerebral ischemia. Delayed neuronal death in the CA1 of the aged group was much slower than that in the adult group after ischemia/reperfusion (I/R). pERK1/2 immunoreaction was observed in the CA1 region of the sham-operated adult gerbil.

Decreased glucagon-like peptide-1 receptor immunoreactivity in the dentate granule cell layer from adult in the gerbil hippocampus.

In this study, we investigated age-related changes in glucagon-like peptide-1 receptor (GLP-1R) immunoreactivity and its protein levels in the gerbil hippocampus during normal aging. In the postnatal month 3 (PM 3) group, GLP-1R immunoreaction was well observed in neurons, especially pyramidal and non-pyramidal cells in the hippocampus proper, and granule and polymorphic cells in the dentate gyrus. In the hippocampus proper, GLP-1R immunoreactivity in neurons was maintained until PM 24.

Clec14a is specifically expressed in endothelial cells and mediates cell to cell adhesion.

Clec14a is a member of the thrombomodulin (TM) family, but its function has not yet been determined. Here, we report that Clec14a is a plasma membrane protein of endothelial cells (ECs) expressed specifically in the vasculature of mice. Deletion mutant analysis revealed that Clec14a mediates cell-cell adhesion through its C-type lectin-like domain.

The role of peroxisome proliferator-activated receptor γ, and effects of its agonist, rosiglitazone, on transient cerebral ischemic damage.

Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in neurons and glia, and its synthetic agonist, rosiglitazone (RSG), regulates inflammatory process and has neuroprotective effects against neurological disorders. In the present study, we examined the role of PPARγ in the hippocampal CA1 region (CA1) after transient cerebral ischemia and the neuroprotective effects of RSG on ischemic damage. RSG attenuated neuronal damage in the ischemic CA1, not showing perfect neuroprotection: the RSG appeared to delay neuronal death after ischemia/reperfusion (I/R).

Immobilization stress induces endothelial dysfunction by oxidative stress via the activation of the angiotensin II/its type I receptor pathway.

Objective: Psychological stress has been shown to contribute to the development of atherosclerosis; however its underlying mechanism has not been clearly elucidated. We here studied the mechanism by which immobilization stress causes endothelial dysfunction with specific aim of identifying the role of angiotensin II and its type I (AT(1)) receptor signaling pathway.

Methods And Results: Rats (n=30) were subjected to immobilization stress (120 min/day) for 14 days using a restrainer.

Fibronectin and vitronectin induce AP-1-mediated matrix metalloproteinase-9 expression through integrin α(5)β(1)/α(v)β(3)-dependent Akt, ERK and JNK signaling pathways in human umbilical vein endothelial cells.

The activity of matrix metalloproteinases (MMPs), which selectively degrades the extracellular matrix (ECM), is critical in angiogenesis. Conversely, changes in ECM composition/structure alter the expression and activity of MMPs in various cell types. In the present study, we examined whether changes in ECM composition affect MMPs expression/activity of endothelial cells and thereby alter the surrounding ECM structure.

Mel-18, a mammalian Polycomb gene, regulates angiogenic gene expression of endothelial cells.

Mel-18 is a mammalian homolog of Polycomb group (PcG) genes. Microarray analysis revealed that Mel-18 expression was induced during endothelial progenitor cell (EPC) differentiation and correlates with the expression of EC-specific protein markers. Overexpression of Mel-18 promoted EPC differentiation and angiogenic activity of ECs.

Carbon monoxide promotes VEGF expression by increasing HIF-1alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF-1alpha protein.

Carbon monoxide (CO) plays a significant role in vascular functions. We here examined the molecular mechanism by which CO regulates HIF-1 (hypoxia-inducible transcription factor-1)-dependent expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. We found that astrocytes stimulated with CORM-2 (CO-releasing molecule) promoted angiogenesis by increasing VEGF expression and secretion.

Anti-inflammatory activity of n-propyl gallate through down-regulation of NF-κB and JNK pathways.

The present study aimed to assess anti-inflammatory activity and underlying mechanism of n-propyl gallate, the n-propyl ester of gallic acid. n-Propyl gallate was shown to contain anti-inflammatory activity using two experimental animal models, acetic acid-induced permeability model in mice, and air pouch model in rats. It suppressed production of nitric oxide and induction of inducible nitric oxide synthase and cyclooxygenase-2 in the lipopolysaccharide (LPS)-stimulated RAW264.

Molecular imaging of membrane proteins and microfilaments using atomic force microscopy.

Atomic force microscopy (AFM) is an emerging technique for a variety of uses involving the analysis of cells. AFM is widely applied to obtain information about both cellular structural and subcellular events. In particular, a variety of investigations into membrane proteins and microfilaments were performed with AFM.

Receptor activator of nuclear factor kappaB ligand is a novel inducer of tissue factor in macrophages.

Rationale: Although recent studies have suggested a role for the receptor activator of nuclear factor κB ligand (RANKL) in the late stages of atherosclerosis (eg, plaque destabilization and rupture), the underlying mechanisms and subsequent events are unclear.

Objective: Because blood clotting is common after plaque rupture, we hypothesized that RANKL influenced tissue factor (TF) expression and activity to initiate the coagulation cascade.

Methods And Results: RANKL increased the TF mRNA level and procoagulant activity in macrophages, as determined by semiquantitative reverse transcription polymerase chain reaction (semiquantitative RT-PCR) and a chromogenic assay.

Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities.

Heme oxygenases (HOs) are the rate-limiting enzymes in the catabolism of heme into biliverdin, free iron, and carbon monoxide. Two genetically distinct isoforms of HO have been characterized: an inducible form, HO-1, and a constitutively expressed form, HO-2. HO-1 is a kind of stress protein, and thus regarded as a sensitive and reliable indicator of cellular oxidative stress.

Difference of fibroblast growth factor receptor 1 expression among CA1-3 regions of the gerbil hippocampus after transient cerebral ischemia.

Fibroblast growth factors are important regulators of neuronal development. In this study, we observed fibroblast growth factor receptor 1 (FGFR1) immunoreactivity and its protein levels in the hippocampus proper (CA1-3 regions) of the gerbil at various time points after ischemia/reperfusion. In the sham-operated group, FGFR1 immunoreaction was not detected in the hippocampus proper.

Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide.

Lipopolysaccharide (LPS) induces a strong immune response, and pretreatment with low dose of LPS suppresses the production of proinflammatory mediators. In the present study, we investigated the effect of LPS preconditioning on the delayed neuronal death in the gerbil hippocampal CA1 region after 5 min of transient cerebral ischemia. LPS preconditioning showed neuroprotective effects against ischemic damage in the hippocampal CA1 region after ischemic insult: about 92% of neurons in the CA1 region survived in the LPS-treated ischemia group.

Melatonin's protective action against ischemic neuronal damage is associated with up-regulation of the MT2 melatonin receptor.

Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. In the present study, we examined the relationship between the neuroprotective effects of melatonin and the activation of MT2 melatonin receptor in the hippocampal CA1 region (CA1) after transient cerebral ischemia. MT2 immunoreactivity and protein levels were increased in the CA1 after ischemic damage.

Hypothyroid state does not protect but delays neuronal death in the hippocampal CA1 region following transient cerebral ischemia: focus on oxidative stress and gliosis.

We investigated protective effects of hypothyroidism on delayed neuronal death, gliosis, lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) in the gerbil hippocampal CA1 region (CA1) after 5 min of transient cerebral ischemia. The hypothyroidism was induced by 0.025% methimazole treatment.

Cancer/testis antigen CAGE exerts negative regulation on p53 expression through HDAC2 and confers resistance to anti-cancer drugs.

The role of the cancer/testis antigen CAGE in drug resistance was investigated. The drug-resistant human melanoma Malme3M (Malme3M(R)) and the human hepatic cancer cell line SNU387 (SNU387(R)) showed in vivo drug resistance and CAGE induction. Induction of CAGE resulted from decreased expression and thereby displacement of DNA methyltransferase 1(DNMT1) from CAGE promoter sequences.

Arylalkylamine N-acetyltransferase (AANAT) is expressed in astrocytes and melatonin treatment maintains AANAT in the gerbil hippocampus induced by transient cerebral ischemia.

Melatonin is synthesized from serotonin by the action of arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase. In this study, we observed cellular changes of arylalkylamine N-acetyltransferase (EC 2.3.