Effect of danazol on NK cells and cytokines in the mouse uterus.
Danazol, which has been used as a medicine for endometriosis, has a valid effect in pretreatment of patients receiving in vitro fertilization and embryo transfer, although its reproductive mechanism remains unclear. BALB/c mice were subcutaneously injected with danazol for 2 weeks. Blood and uteri were collected and cytokines were assayed. Following danazol treatment, an increase in pregnancy ratio was evident that was accompanied by up-regulation in serum macrophage-colony stimulating factor (M-CSF). RT-PCR analysis revealed that expression of M-CSF and Ly49, a phenotypic marker of natural killer (NK) cells, was up-regulated in the uteri of the danazol-treated mice. In immunohistochemical analysis, M-CSF and Ly49, together with alpha5 integrin, were clearly detected in the endometrium of the danazol-treated mice with very similar pattern of localization. These results suggest that danazol has an effect to promote pregnancy that induces recruitment of NK cells and a concomitant increase in the expression of M-CSF and alpha5 integrin in the uterus.
Kusakabe
Ken
K
Department of Anatomy and Cell Biology, Division of Basic Medicine 1, Osaka Medical College, Japan.
Morishima
Shoko
S
Nakamuta
Nobuaki
N
Li
Zhong-Lian
ZL
Otsuki
Yoshinori
Y
D000818:Animals; D016207:Cytokines / Q000097:blood*; D003613:Danazol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D018873:Pregnancy Rate; D012098:Reproduction / Q000187:drug effects; D014599:Uterus / Q000166:cytology* / Q000276:immunology
D016207:Cytokines; D004965:Estrogen Antagonists; D018664:Interleukin-12; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D003613:Danazol