17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

Abstract

In order to clarify the effects of 17β-estradiol (E2) on natural killer (NK) cells and the possibly regulatory mechanisms, we obtained highly purified and viable NK cells from C57BL/6J mouse spleen by a magnetic cell sorter (MACS). These cells were treated with E2 and then their cytotoxicity and proliferative capacity were examined. To further investigate the mechanisms on the effect of E2 on NK cells, expressions of activationassociated markers (CD69, CD122) and inhibitory receptors (CD94, Ly49), and intracellular cytokine production were analyzed. At last, we performed the cDNA microarray to explore the possible involved genes. We found that E2 could suppress NK cell cytotoxicity and proliferative capacity in vitro. E2 reduced NK cell cytotoxicity and proliferative capacity, which may be through influencing the phenotypes and cytokine expression of NK cells, mainly involving CD94 and IFN-γ. Furthermore, regulation of Stat4, Fyn, Sh2d1a, Eat2, Cd244, Irf1, Runx1, Irf7, Irf5, Esrra and Nr5a1 genes may be related to the cytotoxicity, proliferation and cytokine production of E2-mediated purified NK cells. Cellular & Molecular Immunology. 2008;5(5):357-364.

Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17

“…17b-estradiol can suppress the cytotoxicity and proliferative capacity of murine splenic NK1.1 in vitro. 32 The interaction between NKG2DL and NKG2D plays an important role in immune surveillance, and MICA/B are ligands for NKG2D.…”

Glucocorticoid Receptor Mediates the Effect of Progesterone on Uterine Natural Killer Cells

“…11 Some reports also indicated that P4 can suppress lytic activity of uNK cells and enhanced the expansion of the CD56 + population in endometrial leucocytes. 11 Some reports also indicated that P4 can suppress lytic activity of uNK cells and enhanced the expansion of the CD56 + population in endometrial leucocytes.…”

“…Our previous study showed that 17b-Estradiol (E2) could suppress cytotoxicity and proliferative capacity of murine splenic NK1.1 + cells. 11 Some reports also indicated that P4 can suppress lytic activity of uNK cells and enhanced the expansion of the CD56 + population in endometrial leucocytes. 12,13 Although peripheral blood NK cells express progesterone receptors (PR), 14 uNK cells do not express PR in both women and mice.…”

Neuro-endocrine-immune Crosstalk and Implications for Cancer Therapy

“…Experimental studies imply that, on one hand, "low-dose" estrogen increases antibody production [41][42][43] and autoimmunity [44,45], while on the other hand, it decreases T-cell mediated delayed-type hypersensitivity (DTH) [41,[46][47][48], suppresses leukocyte production in the bone marrow and granulocyte-mediated inflammation [49] as well as natural killer (NK)-cell mediated cytotoxicity [43,50,51]. Mammalian cells express 2 receptor isoforms for estrogen receptor (ER), ERα and ERβ [52], although their relative contribution to estrogen-mediated changes in hematopoiesis is still under considerable debate [53].…”