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Human Chorionic Gonadotropin (HCG) Activates Monocytes to Produce Interleukin-8 via a Different Pathway from Luteinizing Hormone/HCG Receptor System

Department of Gynecology and Obstetrics, Faculty of Medicine (K.K., H.F., K.T., S.Y., Y.S., T.H., S.F.), Institute for Virus Research (M.U.), and Institute for Frontier Medical Science (M.M.), Kyoto University, Sakyo-ku, Kyoto 606-8507; and Department of Obstetrics and Gynecology (H.E., T.N.), Japan Baptist Hospital, Sakyo-ku, Kyoto 606-8273, Japan

Address all correspondence and requests for reprints to: Hiroshi Fujiwara, M.D., Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail: fuji{at}kuhp.kyoto-u.ac.jp.

Abstract

To investigate immune-endocrine interactions between the embryo and the mother early in pregnancy, we examined the effects of human chorionic gonadotropin (HCG) on IL-8 production by peripheral blood mononuclear cells (PBMC). Recombinant HCG promoted IL-8 secretion by PBMC derived from nonpregnant women. The induction of IL-8 mRNA expression was observed after 30 min of HCG stimulation. Adsorption of the HCG with anti-HCG antibodies confirmed the specificity of this effect. The translocation of nuclear factor B into the nucleus and subsequent IL-8 production were observed mainly in monocytes, and IL-8 production was reduced when a proteasome inhibitor was added to inactivate nuclear factor B. Although fluorescein isothiocyanate-labeled HCG was bound to the majority of monocytes, cell surface expression of HCG receptor was hardly detected. IL-8 production by HCG was not affected by inhibitors of protein kinases A and C. In contrast, this stimulation was attenuated by D-mannose, which inhibits binding to C-type lectins. The basal IL-8 production by PBMC from women early in pregnancy was significantly elevated, compared with that from nonpregnant women.

This study showed that human monocytes respond to HCG and secrete IL-8 through a pathway different from the HCG receptor system, suggesting that this glycoprotein hormone can react with not only endocrine cells but also immune cells early in pregnancy, probably via primitive systems such as C-type lectins.

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