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

被引:99
作者
LI, Y
MATSUZAKI, N
MASUHIRO, K
KAMEDA, T
TANIGUCHI, T
SAJI, F
YONE, K
TANIZAWA, O
机构
[1] OSAKA UNIV, SCH MED,DEPT OBSTET & GYNECOL,1-1-50 FUKUSHIMA, FUKUSHIMA KU, OSAKA 553, JAPAN
[2] OSAKA ROSAI HOSP, SAKAI, OSAKA 59001, JAPAN
[3] TEIJIN LTD, TEIJIN TOKYO RES CTR, BIOTECHNOL RES LABS, HINO, TOKYO 191, JAPAN
关键词
D O I
10.1210/jc.74.1.184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:184 / 191
页数:8
相关论文
共 38 条
[1]   RELEASE OF MULTIPLE HORMONES BY A DIRECT ACTION OF INTERLEUKIN-1 ON PITUITARY-CELLS [J].
BERNTON, EW ;
BEACH, JE ;
HOLADAY, JW ;
SMALLRIDGE, RC ;
FEIN, HG .
SCIENCE, 1987, 238 (4826) :519-521
[2]   IDENTIFICATION OF 2 TYPES OF TUMOR-NECROSIS-FACTOR RECEPTORS ON HUMAN CELL-LINES BY MONOCLONAL-ANTIBODIES [J].
BROCKHAUS, M ;
SCHOENFELD, HJ ;
SCHLAEGER, EJ ;
HUNZIKER, W ;
LESSLAUER, W ;
LOETSCHER, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (08) :3127-3131
[3]   CHARACTERIZATION OF THE TUMOR NECROSIS FACTOR RECEPTOR IN HUMAN-PLACENTA [J].
EADES, DK ;
CORNELIUS, P ;
PEKALA, PH .
PLACENTA, 1988, 9 (03) :247-251
[4]  
ELIAS JA, 1987, J IMMUNOL, V138, P3812
[5]  
ELIAS JA, 1990, J IMMUNOL, V145, P161
[6]  
FLYNN A, 1982, SCIENCE, V218, P457
[7]   PERIPHERAL-BLOOD MONOCYTE MACROPHAGES AND SERUM TUMOR NECROSIS FACTOR IN KAWASAKI DISEASE [J].
FURUKAWA, S ;
MATSUBARA, T ;
JUJOH, K ;
YONE, K ;
SUGAWARA, T ;
SASAI, K ;
KATO, H ;
YABUTA, K .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1988, 48 (02) :247-251
[8]   TUMOR NECROSIS FACTOR-ALPHA INHIBITS THE HORMONAL RESPONSE OF THE PITUITARY-GLAND TO HYPOTHALAMIC RELEASING FACTORS [J].
GAILLARD, RC ;
TURNILL, D ;
SAPPINO, P ;
MULLER, AF .
ENDOCRINOLOGY, 1990, 127 (01) :101-106
[9]   PURIFICATION TO HOMOGENEITY AND CHARACTERIZATION OF HUMAN B-CELL DIFFERENTIATION FACTOR (BCDF OR BSFP-2) [J].
HIRANO, T ;
TAGA, T ;
NAKANO, N ;
YASUKAWA, K ;
KASHIWAMURA, S ;
SHIMIZU, K ;
NAKAJIMA, K ;
PYUN, KH ;
KISHIMOTO, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (16) :5490-5494
[10]  
HIRATA Y, 1989, J IMMUNOL, V143, P2900