THE ROLE OF CYTOKINES FOR MAINTENANCE OF PREGNANCY

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Varieties of cytokine receptors are present on trophoblast infiltraing into the decidua, and many cytokines are produced in the decidua. In the present study, we examined physiological effects of these cytokines on the trophoblast in vitro, and found that growth of the trophoblast was accelerated with M-CSF,SCF,HGF and EGF.Interestingly, all of the receptors for these cytokines contain a tyrosine kinase domain in themselves. This finding indicates the importance of tyrosine kinase in the growth of the trophoblast. On the other hand, it was concluded that EGF and M-CSF promote the differentiation, SGF suppresses thedifferentiation on the contraray, and HGF dose not affect the differentiation atall. In other words, it was clarified that tyrosine kinase is used as a common pathway in acceleration of growth of the trophoblast, but different complicated signal transduction pathways for induction of differentiation exist.In the present study, we also clarified production of varieties of cyto … More kinesby CD16-CD56 ^<bright>NK cells that markedly proloferated in the decidua in the early stage of pregnancy. Among them, M-CSF was showm tocontribute to the growth and differentiation of the prophoblast. Since angiogenesis effect of IL-8 has been reported, its participation in angiogenesis at the time of implantation can be expected. When GM-CSF was administrered to abortive mice, CBA*DBA_2, the abortion rate decreased. Hence, GM-CSF secreted by decicual CD16^- CD56^<bright> NK cells appear to play some role in implantation. Since IFN and TNF alpha promotethe expression of MHC Class I molecule and may have been protected from the attack by NK cells. TGF beta produced by decidual NK cells and trophoblast suppressed production of IL-2 decidual T-cells, and appeared to protect the prophoblast from the attack by NK cells, and as a result TGF beta contribute to maintanence of pregnancy. In summary, cytokines appear to cotribute to the maintanence of pregnancy by controlling the immune system and promoting the function of the trophoblast at the implantation site. Less