The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

Tomoyasu Nishimura, Xiaomin Zhao, Huixian Gan, Shigeo Koyasu, Heinz G. Remold

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Previously, we reported that in macrophages (Mφs), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE2 receptor EP2. However, human Mφs also express EP4, a PGE2 receptor functionally closely related to EP2 that also couples to stimulatory guanine nucleotide binding protein, but the functional differences between EP2 and EP4 in Mtb-infected Mφs have been unclear. EP4 antagonist addition to H37Rainfected Mφs inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase- 1 (mPGES-1), which are involved in PGE2 production. Moreover, H37Ra infection induced PGE2 production through the Toll-like receptor (TLR) 2/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection was increased after additional stimulation with EP4 agonist. Hence, in Mtb-infected Mφs, PGE2 production induced by pathogen recognition receptors/p38 MAPK signaling is upregulated by EP4-triggered signaling to maintain an effective PGE2 concentration.-Nishimura, T., Zhao, X., Gan, H., Koyasu, S., and Remold, H. G. The prostaglandin E 2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis.

Original languageEnglish
Pages (from-to)3827-3836
Number of pages10
JournalFASEB Journal
Volume27
Issue number9
DOIs
Publication statusPublished - 2013 Sep

Fingerprint

Prostaglandin Receptors
Macrophages
Mycobacterium tuberculosis
Dinoprostone
Feedback
Mycobacterium Infections
p38 Mitogen-Activated Protein Kinases
Cyclooxygenase 2
Prostaglandins E
Receptors, Prostaglandin E, EP2 Subtype
Toll-Like Receptor 2
Guanine Nucleotides
Pathogens
Infection
Permeability
Carrier Proteins
Necrosis

Keywords

  • Cyclooxygenase 2
  • P38 mitogen-activated protein kinase
  • Toll-like receptor 2

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis. / Nishimura, Tomoyasu; Zhao, Xiaomin; Gan, Huixian; Koyasu, Shigeo; Remold, Heinz G.

In: FASEB Journal, Vol. 27, No. 9, 09.2013, p. 3827-3836.

Research output: Contribution to journalArticle

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