title: Modulation of 17beta-estradiol on the number and cytotoxicity of NK cells in vivo related to MCM and activating receptors.
abstract: Natural killer (NK) cells are key components of immune systems and their activities could be regulated by sex hormones. In the present study we investigate the effects of estrogen on the number and cytotoxic activity of NK cells in vivo. The number and cytotoxicity of NK cells in four groups (control, sham+vehicle, Ovx+vehicle and Ovx+E2) were determined. The results showed that 17beta-estradiol (E2) increased the number of NK cells, but reduced their cytotoxicity. The increase of NK cells proportions by E2 may be mediated by up-regulating the expression of MCM7 and MCM10 proteins, which are required for DNA replication licensing in cell proliferation. The suppressed cytotoxicity of splenic NK cells by E2 may be attributable to the down-regulation of NK cells activating receptors-CD69, NKp46, NKG2DL and 2B4 (CD244), which directly inhibited NK cell activation, resulting in the reduced secretion of the soluble factors-granzyme B and FasL. INF-gamma might also act as a negative regulator in the low cytotoxicity of NK cells. In addition, the number of the NK cells is not parallel to their cytotoxicity with a long-term exposure to E2 in vivo. These results suggest that E2-mediated low cytotoxicity of NK cells may regulate host immune response in pregnancy and some female predominant diseases.
authors.affiliation: Immunology and Reproductive Biology Lab of Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, People's Republic of China.
authors.forename: Sha
authors.initials: S
authors.lastname: Hao
authors.forename: Junli
authors.initials: J
authors.lastname: Zhao
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhou
authors.forename: Shuli
authors.initials: S
authors.lastname: Zhao
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011971:Receptors, Immunologic / Q000235:genetics*; D055607:Receptors, Natural Killer Cell; D000071176:Signaling Lymphocytic Activation Molecule Family; D013154:Spleen / Q000166:cytology; D014599:Uterus / Q000187:drug effects; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004958:Estradiol; D007371:Interferon-gamma; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000071176:Signaling Lymphocytic Activation Molecule Family; D000099192:CD69 Antigens; C490007:Cd244a protein, mouse; C491086:Mcm7 protein, mouse