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

Autor: Tetsuo Nagasaka, Koji Tamakoshi, Shigehiko Mizutani, Seiji Nomura, Masafumi Tsujimoto, Fumitaka Kikkawa, Tomomi Ito, Yoko Ikoma, Mayumi Okada, Y. Katsumata, Kumi Iwanaga, Masayuki Nakata
Rok vydání: 2003
Předmět:
Embryology
Transcription
Genetic
Recombinant Fusion Proteins
medicine.medical_treatment
Cycloheximide
Biology
Transfection
Gene Expression Regulation
Enzymologic
Proinflammatory cytokine
chemistry.chemical_compound
Western blot
Genes
Reporter
Pregnancy
Gene expression
Tumor Cells
Cultured
Genetics
medicine
Humans
Cystinyl Aminopeptidase
Choriocarcinoma
RNA
Messenger
Luciferases
Molecular Biology
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
digestive
oral
and skin physiology
Receptors
Interleukin-1
Obstetrics and Gynecology
Promoter
Cell Biology
equipment and supplies
medicine.disease
Molecular biology
Gene Expression Regulation
Neoplastic
Cytokine
Reproductive Medicine
chemistry
Cell culture
Uterine Neoplasms
Female
human activities
Interleukin-1
Developmental Biology
Zdroj: Molecular Human Reproduction. 9:103-110
ISSN: 1460-2407
Popis: 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-1beta (IL-1beta) 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-1beta 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-1beta-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-1beta induces P-LAP in the trophoblasts, possibly via other de-novo protein synthesis, which contradicted our initial hypothesis.
Databáze: OpenAIRE
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