Publication Date:
2013-08-30
Description:
Prostaglandin E 2 (PGE 2 ) is an important biological mediator involved in the defense against Mycobacterium tuberculosis ( Mtb ) infection. Previously, we reported that in macrophages (Ms), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE 2 receptor EP2. However, human Ms also express EP4, a PGE 2 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 Ms have been unclear. EP4 antagonist addition to H37Ra-infected Ms inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE 2 production. Moreover, H37Ra infection induced PGE 2 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 Ms, PGE 2 production induced by pathogen recognition receptors/p38 MAPK signaling is up-regulated by EP4-triggered signaling to maintain an effective PGE 2 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 E 2 production in human macrophages infected with Mycobacterium tuberculosis .
Print ISSN:
0892-6638
Electronic ISSN:
1530-6860
Topics:
Biology
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