The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis
| Autor: | Tomoyasu Nishimura, Shigeo Koyasu, Huixian Gan, Heinz G. Remold, Xiaomin Zhao |
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| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
Prostaglandin E2 receptor medicine.medical_treatment Immunoblotting Biology Biochemistry p38 Mitogen-Activated Protein Kinases Dinoprostone Research Communications Genetics medicine Humans Prostaglandin E2 Receptor Protein kinase A Molecular Biology Reverse Transcriptase Polymerase Chain Reaction Macrophages Mycobacterium tuberculosis Toll-Like Receptor 2 Cell biology TLR2 Cyclooxygenase 2 Immunology lipids (amino acids peptides and proteins) Signal transduction Receptors Prostaglandin E EP4 Subtype Biotechnology medicine.drug Prostaglandin E Signal Transduction |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 27(9) |
| ISSN: | 1530-6860 |
| Popis: | 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 H37Ra-infected 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 up-regulated by EP4-triggered signaling to maintain an effective PGE2 concentration.—Nishimura, T., Zhao, X., Gan, H., Koyasu, S., and Remold, H. G. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis. |
| Databáze: | OpenAIRE |
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