ABSTRACT
BACKGROUND/AIM: Natural killer (NK) cell receptors affect the NK cell-mediated elimination of malignant cells. In this experimental study the effect of Zoledronic acid (ZOL) was investigated on the expression of NK activating- (NKP46 and NKG2D) and inhibitory (KIR2DL1) receptors by Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from breast cancer (BC) patients. MATERIALS AND METHODS: Peripheral blood mononuclear cell-extracted RNA from thirty breast cancer women and twenty-five healthy subjects was analyzed for gene expression of NKP46, NKG2D and KIR2DL1 using real time-PCR. Then, the PBMCs from BC patients were cultured in the presence of PHA with 5 µg/ml, 10 or 20 µg/ml of ZOL for 32 hours and expression of the aforementioned receptors was determined. RESULTS: Expression of NKP46, NKG2D and NKP46/KIR2DL1 ratio in BC women were lower than healthy group (P<0.01, P<0.04 and P<0.05, respectively). NKP46 expression was up-regulated by PHA-stimulated PBMCs treated with 10 µg/ml and 20 µg/ml of ZOL compared with PHA-stimulated cultures (P<0.01 and P<0.05, respectively). NKG2D expression remarkably increased by PHA-stimulated cultures treated with 5 µg/ml, 10 µg/ml and 20 µg/ml of ZOL compared with PHA-stimulated cultures (P<0.05 and P<0.02 and P<0.04, respectively). CONCLUSION: Expression of NK cell-related activating receptors decreased in BC patients. ZOL can improve the expression of NK activating receptors.
Subject(s)
Breast Neoplasms , NK Cell Lectin-Like Receptor Subfamily K , Natural Cytotoxicity Triggering Receptor 1 , Receptors, KIR2DL1 , Zoledronic Acid , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Female , Humans , Leukocytes, Mononuclear/metabolism , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Natural Cytotoxicity Triggering Receptor 1/metabolism , Phytohemagglutinins/pharmacology , Receptors, KIR2DL1/metabolism , Receptors, Natural Killer Cell/metabolism , Zoledronic Acid/therapeutic useABSTRACT
BACKGROUND: The imbalance between Th2 and Treg cells plays fundamental role in the pathogenesis of allergic asthma. The current study aimed at assessing the expression of some Th2 and Treg cell-related parameters in patients with allergic asthma. MATERIAL AND METHODS: The serum and peripheral blood mononuclear cell (PBMC) samples were collected from 30 patients with asthma and 36 healthy subjects. The serum levels of transforming growth factor (TGF)-ß, interleukin (IL)-4, as well as the expression levels of GATA3 and FOXP3 genes in PBMCs were determined by the enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. The PBMCs were cultured for 48 hours with/without phytohemagglutinin (PHA) stimulation. The TGF-ß and IL-4 levels in supernatants were also determined. RESULTS: The serum levels of IL-4, the expression level of GATA3, and GATA3/FOXP3 ratio in patients with asthma were significantly higher than healthy subjects (P <0.002, P <0.001, and P <0.004, respectively). The FOXP3 expression did no differ between the two groups. The serum level of TGF-ß as well as its secretion profile in non-stimulated and stimulated PBMCs isolated from patients with asthma were significantly higher than those of the controls (P <0.03, P <0.001, and P <0.001, respectively). The serum TGF-ß levels in severe asthma were significantly higher than moderate asthma; whereas the TGF-ß secretion by PHA-stimulated PBMCs isolated from moderate asthma was higher than that of severe pattern of the disease (P <0.001 and P <0.05, respectively). The GTAT3/FOXP3 expression ratio in moderate asthma was significantly higher than severe form (P <0.04). CONCLUSION: The results confirmed a Th2 cell-biased pattern and possible contribution of TGF-ß in allergic asthma. TGF-ß may have different expression patterns in moderate and severe asthma and the two forms of the disease may have differences in some main immunological parameters.
