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Molecular Human Reproduction, Vol. 9, No. 2, 103-110, February 2003
© 2003 European Society of Human Reproduction and Embryology

Article

Interleukin-1ß stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells

Submitted on September 20, 2002; accepted on November 25, 2002

Yoko Ikoma1, Seiji Nomura1,5, Tomomi Ito1, Yoshinari Katsumata1, Masayuki Nakata1, Kumi Iwanaga1, Mayumi Okada1, Fumitaka Kikkawa1, Koji Tamakoshi2, Tetsuo Nagasaka3, Masafumi Tsujimoto4 and Shigehiko Mizutani1

Departments of 1 Obstetrics and Gynecology and 2 Public Health, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, 3 Division of Pathology, Clinical laboratory, Nagoya University Hospital, Nagoya, 466-8560 and 4 Laboratory of Cellular Biochemistry, RIKEN (Institute of Physical and Chemical Research), Wako, 351-0148, Japan

5 To whom correspondence should be addressed. e-mail: snomura{at}med.nagoya-u.ac.jp

In addition to prostaglandins, inflammatory cytokines induce uterine contraction via oxytocin (OT). Placental leucine aminopeptidase (P-LAP), an oxytocinase that is identical to cystine aminopeptidase, destroys OT activity. Patients with spontaneous preterm delivery have higher concentrations of inflammatory cytokines and lower P-LAP activities than those with normal delivery. In addition, the P-LAP promoter region contains putative binding sites for cytokine-induced transcription factors. We therefore postulated that inflammatory cytokines suppress P-LAP expression and examined this notion using BeWo choriocarcinoma cells cultured in the presence of cytokines. However, interleukin-1ß (IL-1ß) increased P-LAP activity in a time- and dose-dependent manner. Furthermore, Western blot analysis showed a dose-dependent increase of P-LAP proteins. We also detected IL-1 type I receptor mRNA in BeWo cells by RT–PCR. Semi-quantitative RT–PCR and Southern blot analysis showed that IL-1ß also increased P-LAP mRNA, which was abrogated by prior exposure to cycloheximide. Luciferase assays did not reveal any regulatory regions that could explain IL-1ß-induced P-LAP mRNA accumulation within 1.1 kb upstream of the P-LAP gene. Immunohistochemical analysis of human placenta with chorioamnionitis demonstrated prominent P-LAP staining at sites of abundant inflammatory cell infiltration.These findings indicated that prolonged exposure to IL-1ß induces P-LAP in the trophoblasts, possibly via other de-novo protein synthesis, which contradicted our initial hypothesis.

Key words: aminopeptidase/cytokines/oxytocin/placenta/promoter


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B. Thongsong, R. K. Subramanian, V. Ganapathy, and P. D. Prasad
Inhibition of Amino Acid Transport System A by Interleukin-1{beta} in Trophoblasts
Reproductive Sciences, October 1, 2005; 12(7): 495 - 503.
[Abstract] [PDF]


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