In vitro inhibition of enterobacteria-reactive CD4+CD25- T cells and suppression of immunoinflammatory colitis in mice by the novel immunomodulatory agent VGX-1027.

VGX-1027 is an isozaxoline compound that has recently been found to primarily target the function of murine macrophages but not of T cells, inhibiting secretion of tumor necrosis factor (TNF)-alpha in response to different Toll-like receptor agonists in vitro and in vivo. The well-defined role of innate immunity in inflammatory bowel diseases prompted us to consider the use of VGX-1027 in these diseases leading us to in vitro and in vivo test the drug in related experimental conditions. These consist, respectively, of the proliferation assay of CD4+CD25- T cells to enterobacteria, and the acute inflammatory colitis induced in mice by intracolonic challenge with dinitrobenzene sulfonic acid.

Trail interacts redundantly with nitric oxide in rat astrocytes: potential contribution to neurodegenerative processes.

The proapoptotic cytokine TRAIL has been shown to enhance amyloid-beta-dependent neurotoxicity. Here are reported interactions between TRAIL and nitric oxide (NO) in cultured rat astrocytes in vitro. Rat astrocytes expressed all TRAIL receptor mRNAs and proteins.

Adrenomedullin modulates COX-2 and HGF expression in reserpine-injuried gastric mucosa in the rat.

Here we show the increased hepatocyte growth factor (HGF) and cyclooxygenase-2 (COX-2) expression in gastric mucosa of rats which have developed a reserpine-induced ulcer. Such an increase of HGF and COX-2 expression was blunted in rats pretreated with adrenomedullin. Pretreatment with adrenomedullin and the adrenomedullin22-52 fragment did not result in changes of HGF and COX-2 expression, compared to the reserpine and adrenomedullin treated group.

Supplementation of L-arginine prevents glucocorticoid-induced reduction of bone growth and bone turnover abnormalities in a growing rat model.

The present study was designed to evaluate the effects of glucocorticoid (GC) treatment on bone turnover and bone mineral density in the growing rat. Because of the recent evidence that nitric oxide (NO) can counteract prednisolone-induced bone loss in mature rats, we examined the effect on bone of the NO donor L: -arginine in young male rats, in which bone mass is increased by the same biological mechanism as in children and adolescents. Thirty-six 10-week-old Sprague-Dawley male rats were assigned to six groups of six animals each, and treated for 4 weeks with either vehicle (once a week subcutaneous injection of 100 microl of sesame oil); prednisolone sodium succinate, 5 mg/kg, 5 days per week by intramuscular injection (i.

Growth hormone protects human lymphocytes from irradiation-induced cell death.

1. Undesired effects of cancer radiotherapy mainly affect the hematopoietic system. Growth hormone (GH) participates in both hematopoiesis and modulation of the immune response.