Concentration-dependent noncysteinyl leukotriene type 1 receptor-mediated inhibitory activity of leukotriene receptor antagonists.

The use of cysteinyl leukotriene receptor antagonists (LTRAs) for asthma therapy has been associated with a significant degree of interpatient variability in response to treatment. Some of that variability may be attributable to noncysteinyl leukotriene type 1 receptor (CysLT(1))-mediated inhibitory mechanisms that have been demonstrated for this group of drugs. We used a model of CysLT(1) signaling in human monocytes to characterize CysLT(1)-dependent and -independent anti-inflammatory activity of two chemically different, clinically relevant LTRAs (montelukast and zafirlukast).

Cytosolic phospholipase A2alpha activation induced by S1P is mediated by the S1P3 receptor in lung epithelial cells.

Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activation is a regulatory step in the control of arachidonic acid (AA) liberation for eicosanoid formation. Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator involved in the regulation of many important proinflammatory processes and has been found in the airways of asthmatic subjects. We investigated the mechanism of S1P-induced AA release and determined the involvement of cPLA(2)alpha in these events in A549 human lung epithelial cells.

IL-10 inhibits cysteinyl leukotriene-induced activation of human monocytes and monocyte-derived dendritic cells.

The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells.

Leukotriene D(4) induces gene expression in human monocytes through cysteinyl leukotriene type I receptor.

Background: Cysteinyl leukotrienes (CysLTs) are important mediators of innate immune responsiveness and chronic inflammatory diseases. CysLTs acting through CysLT receptors can influence the migration and activity of cells, such as eosinophils, monocytes, and dendritic cells.

Objective: We sought to determine the gene expression signature of human monocytes in response to CysLTs and to elucidate the signaling pathways involved in monocyte activation.

IFN-gamma induces cysteinyl leukotriene receptor 2 expression and enhances the responsiveness of human endothelial cells to cysteinyl leukotrienes.

Cysteinyl leukotrienes (cysLTs) are important mediators of cell trafficking and innate immune responses, involved in the pathogenesis of inflammatory processes, i.e., atherosclerosis, pulmonary fibrosis, and bronchial asthma.

N-(4-hydroxyphenyl)retinamide induces apoptosis in human retinal pigment epithelial cells: retinoic acid receptors regulate apoptosis, reactive oxygen species generation, and the expression of heme oxygenase-1 and Gadd153.

N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide), a retinoic acid (RA) derivative and a potential cancer preventive agent, is known to exert its chemotherapeutic effects in cancer cells through induction of apoptosis. Earlier work from our laboratory has shown that relatively low concentrations of 4HPR induce neuronal differentiation of cultured human retinal pigment epithelial (ARPE-19) cells (Chen et al., 2003, J Neurochem 84:972-981).

Functional characterization of human cysteinyl leukotriene 1 receptor gene structure.

The 5-lipoxygenase pathway has been strongly implicated in the pathogenesis of chronic inflammatory disorders, such as bronchial asthma and atherosclerosis. Cysteinyl leukotrienes (cysLTs), 5-lipoxygenase pathway products, are recognized now not only as important factors in asthmatic inflammation, but also as mediators of cell trafficking and innate immune responses. To study a role of cysLTs in inflammatory reactions we have characterized the gene structure of human cysteinyl leukotriene receptor type I (cysLT(1)R).

Transforming growth factor-beta induces expression of vascular endothelial growth factor in human retinal pigment epithelial cells: involvement of mitogen-activated protein kinases.

Vascular endothelial growth factor (VEGF) is a major agent in choroidal and retinal neovascularization, events associated with age-related macular degeneration (AMD) and diabetic retinopathy. Retinal pigment epithelium (RPE), strategically located between retina and choroid, plays a critical role in retinal disorders. We have examined the effects of various growth factors on the expression and secretion of VEGF by human retinal pigment epithelial cell cultures (HRPE).