Journal of Clinical Endocrinology & Metabolism, Vol 74, 184-191, Copyright © 1992 by Endocrine Society

ARTICLES

Trophoblast-derived tumor necrosis factor-alpha induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6- receptor-dependent system in the normal human trophoblasts

Y Li, N Matsuzaki, K Masuhiro, T Kameda, T Taniguchi, F Saji, K Yone and O Tanizawa
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.

The titer of tumor necrosis factor-alpha (TNF alpha) secreted by placental blocks was determined by enzyme immunoassay. The source of placental TNF alpha was immunohistochemically demonstrated with monoclonal anti-TNF alpha antibody to be only trophoblasts. Purified trophoblasts produced 174.4 ng/L TNF alpha by 24 h of culture in vitro. To investigate the role of TNF alpha in placental hormonogenesis, purified trophoblasts were stimulated with recombinant TNF alpha (rTNF alpha) to determine the hCG titer by enzyme immunoassay. Trophoblasts stimulated with rTNF alpha released hCG in a dose-dependent fashion with kinetics similar to those of recombinant interleukin-1 (rIL-1)- stimulated trophoblasts. The stimulated trophoblasts released IL-6 before hCG, but failed to show hCG release when pretreated with anti-IL- 6 receptor (anti-IL-6-R) monoclonal antibody PM-1. However, the pretreatment of trophoblasts with PM-1 did not interfere with rTNF alpha-induced IL-6 release, ruling out the possibility of a nonspecific toxic effect of PM-1 on trophoblasts. These results suggest that trophoblast-derived TNF alpha induced IL-6 release and then activated the IL-6-R system in trophoblasts to release hCG. Since IL-1 has also been demonstrated to induce similar release of IL-6 and hCG from trophoblasts, the effects of TNF alpha and IL-1 on these trophoblast functions were also examined. Simultaneous stimulation of trophoblasts with rTNF alpha and gamma IL-1 alpha resulted in synergistic enhancement of IL-6 release, subsequently leading to enhanced hCG release. Collectively, trophoblast-derived TNF alpha and IL-1 synergistically regulated the level of IL-6 secreted by trophoblasts, the magnitude of which determined the level of hCG released by activating the IL-6-R system in trophoblasts.

This article has been cited by other articles:

				H. N. Jones, T. Jansson, and T. L. Powell IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2 Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1228 - C1235. [Abstract] [Full Text] [PDF]

				S.F. de Medeiros and R.J. Norman Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights Hum. Reprod. Update, January 1, 2009; 15(1): 69 - 95. [Abstract] [Full Text] [PDF]

				M.-R. Du, L. Dong, W.-H. Zhou, F.-T. Yan, and D.-J. Li Cyclosporin A Improves Pregnancy Outcome by Promoting Functions of Trophoblasts and Inducing Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings in the Mouse Biol Reprod, May 1, 2007; 76(5): 906 - 914. [Abstract] [Full Text] [PDF]

				C. Leisser, L. Saleh, S. Haider, H. Husslein, S. Sonderegger, and M. Knofler Tumour necrosis factor-{alpha} impairs chorionic gonadotrophin {beta}-subunit expression and cell fusion of human villous cytotrophoblast Mol. Hum. Reprod., October 1, 2006; 12(10): 601 - 609. [Abstract] [Full Text] [PDF]

				S. J. Renaud, L.-M. Postovit, S. K. Macdonald-Goodfellow, G. T. McDonald, J. D. Caldwell, and C. H. Graham Activated Macrophages Inhibit Human Cytotrophoblast Invasiveness In Vitro Biol Reprod, August 1, 2005; 73(2): 237 - 243. [Abstract] [Full Text] [PDF]

				S. Perrier d'Hauterive, C. Charlet-Renard, S. Berndt, M. Dubois, C. Munaut, F. Goffin, M.-T. Hagelstein, A. Noel, A. Hazout, J.-M. Foidart, et al. Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium Hum. Reprod., November 1, 2004; 19(11): 2633 - 2643. [Abstract] [Full Text] [PDF]

				M. A. Turner, S. Vause, and S. L. Greenwood The Regulation of Interleukin-6 Secretion by Prostanoids and Members of the Tumor Necrosis Factor Superfamily in Fresh Villous Fragments of Term Human Placenta Reproductive Sciences, April 1, 2004; 11(3): 141 - 148. [Abstract] [PDF]

				I. Ogata, K. Shimoya, A. Moriyama, Y. Shiki, Y. Matsumura, K. Yamanaka, T. Nobunaga, Y. Tokugawa, T. Kimura, M. Koyama, et al. Oncostatin M is produced during pregnancy by decidual cells and stimulates the release of HCG Mol. Hum. Reprod., August 1, 2000; 6(8): 750 - 757. [Abstract] [Full Text] [PDF]

				D. Chardonnens, P. Cameo, M.L. Aubert, F.P. Pralong, D. Islami, A. Campana, R.C. Gaillard, and P. Bischof Modulation of human cytotrophoblastic leptin secretion by interleukin-1{alpha} and 17{beta}-oestradiol and its effect on HCG secretion Mol. Hum. Reprod., November 1, 1999; 5(11): 1077 - 1082. [Abstract] [Full Text] [PDF]

				K. Shimoya, A. Moriyama, N. Matsuzaki, I. Ogata, M. Koyama, C. Azuma, F. Saji, and Y. Murata Human placental cells show enhanced production of interleukin (IL)-8 in response to lipopolysaccharide (LPS), IL-1 and tumour necrosis factor (TNF)-{alpha}, but not to IL-6 Mol. Hum. Reprod., September 1, 1999; 5(9): 885 - 885. [Abstract] [Full Text] [PDF]

				A. Meisser, D. Chardonnens, A. Campana, and P. Bischof Effects of tumour necrosis factor-{alpha}, interleukin-1 {alpha}, macrophage colony stimulating factor and transforming growth factor ß on trophoblastic matrix metalloproteinases Mol. Hum. Reprod., March 1, 1999; 5(3): 252 - 260. [Abstract] [Full Text] [PDF]

				K.A. Kaufman, J.A. Bowen, A.F. Tsai, J.A. Bluestone, J.S. Hunt, and C. Ober The CTLA-4 gene is expressed in placental fibroblasts Mol. Hum. Reprod., January 1, 1999; 5(1): 84 - 87. [Abstract] [Full Text] [PDF]