Prostaglandin E2 Receptors in Abdominal Aortic Aneurysm and Human Aortic Smooth Muscle Cells

Background: Prostaglandin (PG) E(2) (PGE(2)) appears to have a role in stimulating production of interleukin-6 (IL-6) and apoptosis of smooth muscle cells in diseased aortic tissue. These actions are mediated by cellular receptors for PGE(2) EP receptors.

Objective: This study was undertaken to identify EP receptors associated with production of IL-6 by aortic explants.

Methods: Biopsy specimens of abdominal aortic aneurysm were used for explant culture and preparation of messenger RNA. The presence of EP1, EP2, EP3, and EP4 receptors in tissue and cells was investigated with reverse-transcriptase polymerase chain reaction. IL-6 and cyclic adenosine monophosphate were measured with an enzyme-linked immunosorbent assay.

Results: PGE(2) or 11-deoxy-PGE(1) (EP 2/3/4 agonist) reversed partially the indomethacin suppression of IL-6 secretion from explant cultures, whereas butaprost (EP2 receptor agonist) and sulprostone (EP 1/3 receptor agonist) had no effect. Aortic biopsy specimens expressed EP2, EP3-III, and EP4 receptors. Aortic smooth muscle cells expressed EP2 receptor and four variants of EP3 receptor, ie, EP3-Ib, EP3-II, EP3-III, and EP3-IV, but PGE(2) did not stimulate secretion of IL-6. In contrast, PGE(2) or 11-deoxy-PGE(1) stimulated secretion of IL-6 from aortic macrophages.

Conclusions: In aortic explants, PGE(2) stimulates IL-6 secretion by activation of EP4 receptors, present in macrophages.