Regulation of cytosolic phospholipase A2 expression by cytokines in human amnion cells

Hansen, W. R., Drew, A., Helsby, N., Keelan, J. A., Sato, T. A. and Mitchell, M. D. (1999) Regulation of cytosolic phospholipase A2 expression by cytokines in human amnion cells. Placenta, 20 4: 303-308. doi:10.1053/plac.1998.0376

Author Hansen, W. R.
Drew, A.
Helsby, N.
Keelan, J. A.
Sato, T. A.
Mitchell, M. D.
Title Regulation of cytosolic phospholipase A2 expression by cytokines in human amnion cells
Journal name Placenta   Check publisher's open access policy
ISSN 0143-4004
Publication date 1999-05
Sub-type Article (original research)
DOI 10.1053/plac.1998.0376
Volume 20
Issue 4
Start page 303
End page 308
Total pages 6
Place of publication London, England
Publisher W.B. Saunders
Language eng
Subject 1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Abstract The metabolism of arachidonic acid results in the production of prostaglandins (PGs), which are involved in the initiation of labour at term and preterm. The fetal membranes are a source of pro-inflammatory cytokines which promote increased PG biosynthesis via increased release of arachidonic acid and its conversion to biologically active metabolites such as PGE2and PGF2α. In the amnion, the liberation of arachidonic acid from membrane glycerophospholipid stores can be catalysed by cytosolic phospholipase A2(cPLA2). In amnion-derived WISH cells, the addition of tumour-necrosis factor alpha (TNF-α) (50 ng/ml) provoked a time-dependent increase in the expression of the cPLA2mRNA which was greatest at 8 and 16 h post-treatment (3.62±0.52 and 3.15±0.45-fold of control, N=3). The increase in cPLA2mRNA expression by TNF-α was unaffected by the prior addition of interleukin-4 (IL-4) (10 ng/ml), a known inhibitor of prostaglandin endoperoxide H synthase (PGHS)-2 mRNA and protein expression in WISH cells. TNF-α also increased the level of immunoreactive cPLA2protein in a time-dependent manner with the highest levels evident after 8 and 16 h. As with the mRNA, cPLA2protein levels were unaffected by pre-incubation with IL-4. The inclusion of the cPLA2-specific inhibitor arachidonyl trifluoromethyl ketone (AACOCF3) resulted in a concentration-dependent inhibition of PGE2biosynthesis in WISH cells treated with TNF-α (>95 per cent at 2 μm). We conclude that TNF-α increases the abundance of the cPLA2mRNA and protein in amnion epithelial cells, an effect which plays an important role in amnion PG biosynthesis in the presence of intrauterine infection.
Keyword Tumor-necrosis-factor
Prostaglandin-H Synthase-2
Wish Cells
Inflammatory Mediators
Human Parturition
Preterm Labor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 26 Aug 2010, 12:53:42 EST