Prostaglandin E2 receptors, EP2 and EP4, differentially modulate TNF-α and IL-6 production induced by lipopolysaccharide in mouse peritoneal neutrophils

Hana Yamane, Yukihiko Sugimoto, Satoshi Tanaka, Atsushi Ichikawa

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The expression and function of prostaglandin (PG) E2 receptors were examined in mouse neutrophils exudated into the peritoneal cavity by casein treatment. Expressions of the EP2 and EP4 receptors were detected in neutrophils by Northern blot, but those of EP1 and EP3 receptors were not detected by RT-PCR. EP2-selective agonist, ONO-AE1-259, and EP4-selective agonist, ONO-AE1-329, stimulated cAMP formation in the cells. PGE2 affected the TNF-α and IL-6 production in lipopolysaccharide (LPS)-treated neutrophils; it suppressed the TNF-α production and enhanced the IL-6 production. The PGE2 effects were mimicked by dibutyryl cAMP. This is the first study of the enhancement of IL-6 production by cAMP-elevating reagents in neutrophils. Using neutrophils from EP2- and EP4-deficient mice in combination with EP2- and EP4-selective agonists, it was found that the augmentation of IL-6 was mediated mainly by the EP2 receptor and the suppression of TNF-α by the EP4 receptor and partially by the EP2 receptor. These findings indicate that casein-induced peritoneal neutrophils express Gs-coupled PGE2 receptors, EP2 and EP4, which might differentially regulate the LPS-induced production of TNF-α and IL-6. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)224-228
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume278
Issue number1
DOIs
Publication statusPublished - Nov 11 2000

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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