The “interleukin 1 receptor antagonist” is a partial agonist of prostaglandin synthesis by human decidual cells

Cole, Olatoun F.; Sullivan, Mark; Elder, M. G.

doi:10.1016/0090-6980(93)90068-i

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…We investigated the effect of a p38 inhibitor, SB202190, on the bioactivity of primary cultures of human decidual cells. Stimulation of the cells was performed with IL-1␤, because IL-1␤ is generally considered as one of the physiological triggers of labor (22)(23)(24)(25). We performed a specific radioimmunoassay for PGF 2␣ , which is considered to contribute to the final step of parturition as a potent uterine constrictor and a luteolysis inducer (24,41).…”

Section: Resultsmentioning

confidence: 99%

“…Among the inflammatory cytokines, IL-1␤ is considered to contribute to parturition for the following reasons: the concentration of IL-1␤ is significantly increased in amniotic fluid during labor (20,21); systemic administration of IL-1␤ induces preterm labor and delivery in mice (22); IL-1␤ induces biosynthesis of prostaglandin (PG), one of the mediators of uterine contraction possibly produced by decidual cells, which is associated with induction of cyclooxygenase (COX)-2 (23)(24)(25). Previous studies also demonstrated that IL-1␤ activates p38 in various types of cells (26,27), and that p38 positively regulates the expression of COX-2 at both the transcription and post-transcription levels (27)(28)(29)(30).…”

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confidence: 99%

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Possible Involvement of p38 Mitogen-Activated Protein Kinase in Decidual Function in Parturition

Takanami-Ohnishi

Asada

Tsunoda

et al. 2001

Biochemical and Biophysical Research Communications

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Possible Involvement of p38 Mitogen-Activated Protein Kinase in Decidual Function in Parturition

Takanami-Ohnishi

Asada

Tsunoda

et al. 2001

Biochemical and Biophysical Research Communications

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“…We did not use the IL‐1 receptor antagonist (IL‐1RA) for these studies, as in other investigations 58 . 59 IL‐1RA is an antagonist of the effects of IL‐1β on amnion or chorion, 60 but has partial or full agonist activity on human decidual cells, 61 , 62 and therefore cannot be used to inhibit selectively the receptor‐mediated effects of IL‐1β. Our data (Brown et al 63 …”

Section: Discussionmentioning

confidence: 99%

The production of interleukin‐1β from human fetal membranes is not obligatory for increased prostaglandin output

et al. 1999

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Bacterial endotoxin increased the expression of mRNA (maximal after 4 hr) for interleukin-1beta (IL-1beta) and the release of mature protein from intact human fetal membranes. In contrast, the change in expression of mRNA for type 2 cyclo-oxygenase (COX-2) was biphasic, with peaks after 0.5-1 hr and after 8 hr of culture. An antibody to IL-1beta was without effect after 4 hr of culture, inhibited endotoxin-stimulated prostaglandin E2 (PGE2) production after 8 hr of culture, and caused a parallel decrease in the expression of mRNA for COX-2. We conclude that endotoxin induced the expression of COX-2 through IL-1beta-independent and IL-1beta-dependent mechanisms, and these differences are time dependent. Corticotrophin-releasing hormone (CRH) or platelet-activating factor (PAF) also increased the expression of mRNA for IL-1beta and the release of IL-1beta from some, but not all, fetal membranes. The antibody to IL-1beta did not affect CRH-stimulated or PAF-stimulated PGE2 production or COX-2 expression. We conclude that CRH and PAF can induce the expression of IL-1beta, but this is not obligatory for increased PGE2 release, and the effect of these stimuli on COX-2 expression is a direct, IL-1beta-independent effect.

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“…IL-1 is found in increased levels in the amniotic fluid of women in preterm labour associated with infection (Romero et al 1989) as well as spontaneous labour at term (Romero et al 1990). IL-1ra has been found to prevent IL-1-induced preterm labour in mice (Romero & Tartakovsky 1992), but other workers have reported that, in cultured human decidual cells, IL-1ra can act as a partial agonist of prostaglandin production (Cole et al 1993, Mitchell et al 1993b.…”

Section: Introductionmentioning

confidence: 99%

Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist

Brown

Alvi²,

Elder³

et al. 1998

Journal of Endocrinology

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There is strong evidence for the involvement of inflammatory mediators such as interleukin (IL)-1 in the biochemical mechanisms of parturition. Therefore the effects of the IL-1 family (IL-1 (1 ng/ml), IL-1 (1 ng/ ml) and the IL-1 receptor antagonist (IL-1ra) (10 ng/ml)) on the regulation of prostaglandin synthesis in term human fetal membranes were investigated. It was found that, after 4 h of culture, IL-1 increased prostaglandin E 2 (PGE 2 ) output approximately twofold. This was associated with both a significant increase in cyclo-oxygenase-2 (COX-2) mRNA levels (approximately fourfold compared with control) and translocation of cytoplasmic phospholipase A 2 (cPLA 2 ) from the cytosol to the membrane fraction. IL-1 was less effective than IL-1 at stimulating PGE 2 production through similar mechanisms.IL-1ra had no effect on PGE 2 output. However, in combination treatments, IL-1ra did not inhibit IL-1 -or IL-1 -stimulated PGE 2 output, and increased PGE 2 production further compared with IL-1 alone. IL-1ra decreased IL-1 -induced COX-2 mRNA expression by about half and significantly increased cPLA 2 protein levels, as detected by immunoblotting, when used alone and together with IL-1 . These results suggest that IL-1ra has partial agonist properties when used together with IL-1 and IL-1 in fetal membranes by increasing cPLA 2 protein levels, which leads to an increase in the production of prostaglandins.

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The “interleukin 1 receptor antagonist” is a partial agonist of prostaglandin synthesis by human decidual cells

Cited by 11 publications

References 22 publications

Possible Involvement of p38 Mitogen-Activated Protein Kinase in Decidual Function in Parturition

Possible Involvement of p38 Mitogen-Activated Protein Kinase in Decidual Function in Parturition

The production of interleukin‐1β from human fetal membranes is not obligatory for increased prostaglandin output

Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist

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