The CRTH2 agonist Pyl A prevents lipopolysaccharide‐induced fetal death but induces preterm labour. Issue 3 (13th June 2013)

• Record Type: Journal Article
• Authors: Sykes, Lynne; Herbert, Bronwen R.; MacIntyre, David A.; Hunte, Emma; Ponnampalam, Sathana; Johnson, Mark R.; Teoh, Tiong G.; Bennett, Phillip R.
• Is Part Of: Immunology. Volume 139:Issue 3(2013:Jul.)
• Page Start: 352
• Page End: 365
• Publication Date: 2013-06-13
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12085
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12085-abs-0001"> <title>Summary</title> <p>We have previously demonstrated that the anti‐inflammatory prostaglandin 15‐deoxy‐Δ 12, 14‐prostaglandin J<sub>2</sub> (15dPGJ<sub>2</sub>) delays inflammation‐induced preterm labour in the mouse and improves pup survival through the inhibition of nuclear factor‐κB (NF‐κB) by a mechanism yet to be elucidated. 15dPGJ<sub>2</sub> is an agonist of the second prostaglandin D<sub>2</sub> receptor, chemoattractant receptor homologous to the T helper 2 cell (CRTH2). In human T helper cells CRTH2 agonists induce the production of the anti‐inflammatory interleukins IL‐10 and IL‐4. We hypothesized that CRTH2 is involved in the protective effect of 15dPGJ<sub>2</sub> in inflammation‐induced preterm labour in the murine model. We therefore studied the effects of a specific small molecule CRTH2 agonist on preterm labour and pup survival. An intrauterine injection of lipopolysaccharide (LPS) was administered to CD1 mice at embryonic day 16, ± CRTH2 agonist/vehicle controls. Mice were killed at 4.5 hr to assess fetal wellbeing and to harvest myometrium and pup brain for analysis of NF‐κB, and T helper type 1/2 interleukins. To examine the effects of the CRTH2 agonist on LPS‐induced preterm labour, mice were allowed to labour spontaneously. Direct effects of the CRTH2 agonist on uterine contractility were examined <italic>ex vivo</italic> on contracting myometrial strips. The CRTH2 agonist increased fetal survival from 20 to 100% in LPS‐treated mice, and inhibited circular muscle contractility <italic>ex vivo</italic>. However, it augmented LPS‐induced labour and significantly increased myometrial NF‐κB, IL‐1β, KC‐GRO, interferon‐γ and tumour necrosis factor‐α. This suggests that the action of 15dPGJ<sub>2</sub> is not via CRTH2 and therefore small molecule CRTH2 agonists are not likely to be beneficial for the prevention of inflammation‐induced preterm labour.</p> </abstract>