Effects of interleukin-4 on the expression and activity of prostaglandin endoperoxide H synthase-2 in amnion-derived WISH cells
| Autor: | J.S. Gilmour, Ta Sato, Jeffrey A. Keelan, Mitchell, W.R. Hansen, HC Miller |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Prostaglandin E2 receptor medicine.medical_treatment Gene Expression Prostaglandin Cell Line Proinflammatory cytokine chemistry.chemical_compound Endocrinology Pregnancy Epidermal growth factor Internal medicine medicine Protein biosynthesis Humans Amnion RNA Messenger Molecular Biology Interleukin 4 Membrane Proteins Isoenzymes Kinetics Cytokine chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Cyclooxygenase 1 Female Tumor necrosis factor alpha Interleukin-4 |
| Zdroj: | ResearcherID |
| ISSN: | 1479-6813 0952-5041 |
| DOI: | 10.1677/jme.0.0210317 |
| Popis: | Increased prostaglandin biosynthesis during intrauterine infection may be a possible mechanism by which preterm labour is initiated. Inflammatory cytokines and growth factors are known to stimulate prostaglandin production through an increase in prostaglandin endoperoxide H synthase (PGHS)-2 synthesis and activity. Interleukin-4 (IL-4), an anti-inflammatory cytokine, can downregulate PGHS-2 expression and inhibit prostaglandin production. Therefore, the aims of the current study were to determine the effects of IL-4 on PGHS-1 and PGHS-2 expression in amion-derived WISH cells treated with inflammatory cytokines and growth factors. In WISH cells, near-maximal production of the PGHS-2 mRNA occurred using 5 ng/ml EGF, 1 ng/ml IL-1beta or 50 ng/ml TNF-alpha. Time-course experiments determined that the PGHS-2 mRNA was induced maximally by these stimuli by 1 h. Pretreatment of WISH cells with IL-4 reduced PGHS-2 mRNA levels at 1 h by 67% in cells treated with EGF, 62% in cells treated with IL-1beta and 54% in cells treated with TNF-alpha. Pretreatment with IL-4 more effectively inhibited PGHS-2 expression than simultaneous addition with EGF or IL-1beta but not TNF-alpha. Immunoblot analysis showed a correlation between inhibition of mRNA levels and levels of PGHS-2 protein, although stimulation of PGHS-2 protein production by EGF was undetectable. Levels of PGHS-1 protein and mRNA remained unchanged in all experiments. Increased production of prostaglandin E2 (PGE2) in response to TNF-alpha and IL-1beta treatment was attenuated by IL-4 pretreatment, by 52% and 72%, respectively. No attenuation of EGF-stimulated PGE2 levels was seen. We conclude that IL-4 inhibits PGHS-2 mRNA and protein production in cytokine-stimulated WISH cells, but does not affect EGF-stimulated PGE2 production, suggesting that EGF can induce prostaglandin biosynthesis by a mechanism other than through increased PGHS-2 expression. |
| Databáze: | OpenAIRE |
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