Search results for "Cell Movement"
showing 10 items of 396 documents
Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
2007
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB 1 Rs, identify endoc…
Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2
2012
Tumor vessel dysfunction is a pivotal event in cancer progression. Using an in vivo neovascularization model, we identified G protein–coupled receptor kinase 2 (GRK2) as a key angiogenesis regulator. An impaired angiogenic response involving immature vessels was observed in mice hemizygous for Grk2 or in animals with endothelium-specific Grk2 silencing. ECs isolated from these animals displayed intrinsic alterations in migration, TGF-β signaling, and formation of tubular networks. Remarkably, an altered pattern of vessel growth and maturation was detected in postnatal retinas from endothelium-specific Grk2 knockout animals. Mouse embryos with systemic or endothelium-selective Grk2 ablation …
Diacylglycerol kinase α mediatses 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell …
2011
Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of …
Type II diabetics with macrovascular complications: polymorphonuclear leukocyte (PMN) filtration, PMN membrane fluidity and cytosolic Ca2+ content af…
1998
We evaluated polymorphonuclear (PMN) filtration parameters, membrane fluidity and cytosolic Ca2+ content in 21 normal subjects and in 18 type II diabetics with macrovascular complications (MVC). Evaluations were carried out at baseline and after in vitro activation prolonged for 5 and 15 min. PMA (4-phorbol 12-myristate 13-acetate) and fMLP (N-formyl-methionyl-leucyl-phenylalanine) were used as stimulating agents. TMA-DPH (1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene) was used as fluorescent probe for the membrane fluidity tests and Fura 2-AM for the cytosolic Ca2+ content. A significant variation was evident in PMN filtration parameters at 5 and 15 min. No variation was present i…
Tetralogy of Fallot as a Model to Study Cardiac Progenitor Cell Migration and Differentiation During Heart Development
2009
Tetralogy of Fallot (ToF) has long been considered a congenital disorder that occurs due to environmental alterations during gestation. Recently, several mutated genes have been discovered that are thought to be responsible for the malformations observed in ToF. These genetic mutations, which are microdeletions, are sporadic and are frequently also present in trisomy 21 patients. The ToF malformations can be lethal, but for the last 50 years, surgical repairs that place an artificial patch to repair the four features of ToF have improved the survival of patients with ToF. However, 0.5% to 6% of patients who survive after surgical repair of ToF die of sudden cardiac death caused by ventricul…
Skin response to a carcinogen involves the xenobiotic receptor pregnane X receptor.
2015
Skin is in daily contact with potentially harmful molecules from the environment such as cigarette smoke, automobile emissions, industrial soot and groundwater. Pregnane X receptor (PXR) is a transcription factor expressed in liver and intestine that is activated by xenobiotic chemicals including drugs and environmental pollutants. Topical application of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) enhances Pxr, Cyp1a1, Cyp1b1 and Cyp3a11, but not Ahr expression in the skin. Surprisingly, DMBA-induced Pxr upregulation is largely impaired in Langerin(+) cell-depleted skin, suggesting that DMBA mainly triggers Pxr in Langerin(+) cells. Furthermore, PXR deficiency protects from DN…
Critical role of dipeptidyl peptidase IV in neuropeptide Y-mediated endothelial cell migration in response to wounding
2001
Recently, we have discovered that neuropeptide Y (NPY), a sympathetic neurotransmitter, is also present in human umbilical endothelial cells (HUVECs), and is potently chemotactic and angiogenic by acting on one or several of Y1-Y5 receptors. In HUVECs, NPY is co-localized with dipeptidyl peptidase IV (DPPIV) which cleaves Tyr(1)-Pro(2) from NPY(1-36) to form NPY(3-36) resulting in the formation of a non-Y1 receptor agonist, which remains angiogenic. Presently we studied the effects of DPPIV's blockade using monoclonal antibodies (mAbs) on migration of HUVECs in response to NPY(1-36) or NPY(3-36) following cell wounding. Both peptides caused similar dose-dependent increases in cell migration…
Bafetinib inhibits functional responses of human eosinophils in vitro
2012
Eosinophils play a prominent role in the process of allergic inflammation. Non-receptor associated Lyn tyrosine kinases generate key initial signals in eosinophils. Bafetinib, a specific Abl/Lyn tyrosine kinase inhibitor has shown a potent antiproliferative activity in leukemic cells, but its effects on eosinophils have not been reported. Therefore, we studied the effects of bafetinib on functional and mechanistic responses of isolated human eosinophils. Bafetinib was more potent than non-specific tyrosin kinase comparators genistein and tyrphostin inhibiting superoxide anion triggered by N-formyl-Met-Leu-Phe (fMLF; 100 nM) (−log IC50=7.25±0.04 M; 6.1±0.04 M; and 6.55±0.03 M, respectively).…
Inhibition of the NF-κB Signaling Pathway Mediates the Anti-inflammatory Effects of Petrosaspongiolide M
2003
Petrosaspongiolide M (PT) is a potent secretory phospholipase A(2) inhibitor and anti-inflammatory agent. This marine metabolite reduced the production of nitrite, prostaglandin E(2), and tumor necrosis factor-alpha in the mouse air pouch injected with zymosan. These effects were also observed in mouse peritoneal macrophages stimulated with zymosan. Inhibition of these inflammatory mediators was related to reductions in inducible nitric oxide synthase, cyclo-oxygenase-2, and tumor necrosis factor-alpha expression. Since nuclear factor-kappaB (NF-kappaB) appears to play a central role in the transcriptional regulation of these proteins by macrophages, we investigated the effects of PT on thi…
Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions.
1998
Culture conditions for human dendritic cells (DC) have been developed by several laboratories. Most of these culture methods, however, have used conditions involving fetal calf serum (FCS) to generate DC in the presence of granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4. Recently, alternative culture conditions have been described using an additional stimulation with monocyte-conditioned medium (MCM) and FCS-free media to generate DC. As MCM is a rather undefined cocktail, the yield and quality of DC generated by these cultures varies substantially. We report that a defined cocktail of tumor necrosis factor (TNF)-alpha, IL-1beta and IL-6 equals MCM in its potency to …