ABSTRACT
The role of mast cell mediators on cervical cancer cell migration was assessed using an in vitro assay of scratch wound healing onto monolayers of HPV18-positive cervical carcinoma cells (SW756). Migration of SW756 cells was accelerated by co-culture with the mast cell line LAD2. This effect was inhibited by the H1R antagonist pyrilamine and the cannabinoid agonists 2-arachidonylglycerol (2AG) and Win 55,212-2. Therefore, the specific effects of histamine and cannabinoids on SW756 migration and LAD2 activation were analyzed. Histamine added to the in vitro assay of scratch wound healing either increased or inhibited SW756 migration rate by acting either on H1R or H4R, respectively. Cannabinoids acted on CB1 receptors to inhibit SW756 migration. Supernatants from SW756 cells stimulated LAD2 cell degranulation, which in turn was inhibited by cannabinoids acting via CB2 receptors. RT-PCR showed that SW756 expressed mRNA for CB1, CB2, H1R, H2R, and H4R. On the other hand, LAD2 expressed mRNA for all four HRs and CB2. The results suggest that mast cells could be contributing to cervical cancer cell invasion and spreading by the release of histamine and cannabinoids. Therefore, therapeutic modulation of specific mast cell mediators may be beneficial for cervical cancer treatment.
Subject(s)
Carcinoma/immunology , Mast Cells/immunology , Uterine Cervical Neoplasms/immunology , Cannabinoids/pharmacology , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation , Female , Histamine/immunology , Histamine/pharmacology , Humans , Mast Cells/cytology , Mast Cells/drug effects , RNA, Messenger/metabolism , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/immunology , Receptor, Cannabinoid, CB2/genetics , Receptor, Cannabinoid, CB2/immunology , Receptors, Histamine/genetics , Receptors, Histamine/immunology , Wound Healing , beta-N-Acetylhexosaminidases/immunologyABSTRACT
Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review.
Subject(s)
Mast Cells/metabolism , Parturition/physiology , Uterus/metabolism , Animals , Corticotropin-Releasing Hormone/metabolism , Female , Gonadal Steroid Hormones/metabolism , Humans , Mast Cells/cytology , Muscle Contraction/physiology , Muscle, Smooth/physiology , Oxytocin/metabolism , Pregnancy , Uterus/cytologyABSTRACT
Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review.
ABSTRACT
Chronic incubation with elevated D-glucose reduces adenosine transport in endothelial cells. In this study, exposure of human umbilical vein endothelial cells to 25 mmol/L D-glucose or 100 micromol/L ATP, ATP-gamma-S, or UTP, but not ADP or alpha,beta-methylene ATP, reduced adenosine transport with no change in transport affinity. Inhibition of transport by D-glucose, ATP, and ATP-gamma-S was associated with reduced maximal binding, with no changes in the apparent dissociation constant for nitrobenzylthioinosine (NBMPR). A significant reduction (approximately 60+/-10%, P<0.05; n=6) in the number of human equilibrative NBMPR-sensitive nucleoside transporters (hENT1s) per cell (1.8+/-0.1x10(6) in 5 mmol/L D-glucose) and in hENT1 mRNA levels was observed in cells exposed to D-glucose or ATP-gamma-S. Incubation with elevated D-glucose, but not with D-mannitol, increased the ATP release by 3+/-0.2-fold. The effects of D-glucose and nucleotides on the number and activity of hENT1 and hENT1 mRNA were blocked by reactive blue 2 (nonspecific P2Y purinoceptor antagonist), suramin (Galpha(s) protein inhibitor), or hexokinase but not by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (nonselective P2 purinoceptor antagonist). Our findings demonstrate that inhibition of adenosine transport via hENT1 in endothelial cells cultured in 25 mmol/L D-glucose could be due to stimulation of P2Y2 purinoceptors by ATP, which is released from these cells in response to D-glucose. This could be a mechanism to explain in part the vasodilatation observed in the early stages of diabetes mellitus or in response to D-glucose infusion.
Subject(s)
Adenosine Triphosphate/analogs & derivatives , Adenosine/metabolism , Endothelium, Vascular/metabolism , Glucose/pharmacology , Receptors, Purinergic P2/metabolism , Thioinosine/analogs & derivatives , Thioinosine/pharmacology , Adenosine Diphosphate/pharmacology , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Binding, Competitive/drug effects , Biological Transport/drug effects , Cells, Cultured , Endothelium, Vascular/drug effects , Equilibrative Nucleoside Transporter 1 , Humans , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , RNA, Messenger/metabolism , Receptors, Purinergic P2Y2 , Umbilical Veins , Uridine Triphosphate/pharmacologyABSTRACT
El sulfato de magnesio (MgSO4) ha sido utilizado con éxito en el tratamiento de la preeclampsia y como agente tocolítico en la amenaza de parto prematuro. Tradicionalmente, la terapia consiste en la administración parenteral de MgSO4, sin embargo la base fisiológica de su uso se desconoce. La evidencia experimental señala que tanto la ocitocina como la serotonina y la histamina son capaces de inducir contracciones uterinas al final de la gestación. Nosotros estudiamos el efecto del MgSO4 sobre el efecto uterotónico evocado por estos mediadores y por estímulo eléctrico en una preparación in vitro de cuernos uterinos de ratón suspendidos en un baño de órgano aislado. MgSO4 (6 mEq/lt) redujo significativamente no sólo las contracciones espontáneas sino que también aquellas evocadas por diferentes dosis de exitocina, serotonina e histamina. Sin embargo, la actividad contráctil inducida por estímulo eléctrico no fue afectada por MgSO4 en la dosis utilizada. Postulamos que la eficacia tocolítica del MgSO4 podría ejercerse a través de una competencia con el ion calcio lo que afectaría a la acción uterotónica de algunos mediadores liberados especialmente al final de la gestación
