Viability of SH-SY5Y cells is associated with purinergic P2 receptor expression alterations

To investigate the role of metabotrophic purinergic P2Y receptors in neuroblastoma cell survival, expression of P2 receptors by normal mouse (C57BL/6) brain and human neuroblastoma SH-SY5Y cells was investigated by Western blot and real time PCR studies. Viability of SH-SY5Y cells treated with purinergic receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS) was evaluated by MTT assay and flow cytometry. In the brain samples of C57BL/6 mice, expressions of P2Y4 and P2X7 were significantly reduced, whereas that of P2Y1 was significantly elevated in an age-dependent manner. SH-SY5Y cell viability was significantly reduced and necrotic cell rates were mildly increased by 400 μM suramin and 100 μM PPADS treatment. Antagonist treatment downregulated P2Y1, P2Y2 and P2Y4 and upregulated P2Y6, P2Y12 and P2X7 mRNA levels in SH-SY5Y cells on the 24th hour. These alterations were abolished for all P2 receptors except P2Y1 in the 48th hour. P2Y receptors are expressed by both normal mouse brain and human neuroblastoma cells. Purinergic receptor antagonism interferes with neuroblastoma viability through elevation of necrotic cell death and modulation of P2 receptor expression. P2Y receptors might thus be useful targets for future anti-tumor treatment trials

Natural killer cells: versatile roles in autoimmune and infectious diseases

Natural killer (NK) cells are essential members of innate immunity and they rapidly respond to a variety of insults via cytokine secretion and cytolytic activity. Effector functions of NK cells form an important first line of innate immunity against viral, bacterial and parasitic infections, as well as an important bridge for the activation of adaptive immune responses. The control of NK-cell activation and killing is now understood to be a highly complex system of diverse inhibitory and activatory receptor-ligand interactions, sensing changes in MHC expression. NK cells have a functional role in innate immunity as the primary source of NK-cell-derived immunoregulatory cytokines, which have been identified in target organs of patients suffering from autoimmune diseases, and play a critical role in early defense against infectious agents. This review focuses on recent research of NK cells, summarizing their potential immunoregulatory role in modulating autoimmunity and infectious diseases

PAI-1 and TNF-alpha profiles of adipose tissue in obese cardiovascular disease patients

Obesity as a leading preventable cause of death worldwide is closely linked to cardiovascular disease (CVD). Plasma plasminogen activator inhibitor (PAI)-1, a potent inhibitor of plasminogen activation and fibrinolysis, is increased in many clinical situations associated with high incidence of CVD. In the obesity-linked elevation of PAI-1, evidence points to TNF-alpha as an important regulator of PAI-1 expression in adipose tissue. Background: This study aims to evaluate mediastinal PAI-1 and TNF-alpha mRNA levels in adipose tissues (AT) and compare serum levels in obesity with and without coronary artery disease (CAD). Patients and methods: Obese patients with (n=37) and without CAD (n=20) were included in the study. Results: The serum levels of PAI-1 and TNF-alpha were significantly higher in obese patients with CAD compared to obese patients without CAD. PAI-1 mRNA expression was significantly increased in mediastinal adipose tissue (MAT) of obese patients with CAD compared to those without CAD, TNF-alpha mRNA expressions were found to be higher in EAT (epicardial AT), MAT and SAT (subcutaneous AT) of obese patients with CAD. Conclusions: The study demonstrated a close direct relationship between TNF-alpha and PAI-1. PAI-1 mRNA expression strongly correlated positively with serum TNF-alpha in MAT, and TNF-alpha expressions with PAI-1 serum levels