PMID- 29127186
OWN - NLM
STAT- MEDLINE
DCOM- 20181106
LR  - 20181106
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 32
IP  - 3
DP  - 2018 Mar
TI  - Formyl peptide receptor 2 is regulated by RNA mimics and viruses through an 
      IFN-beta-STAT3-dependent pathway.
PG  - 1468-1478
LID - 10.1096/fj.201700584RR [doi]
AB  - The regulation of host factors is a key strategy employed by viruses to suppress 
      host defense systems and enhance their propagation; however, the mechanisms that 
      underlie this regulation is still unclear. Formyl peptide receptor 2 (FPR2) 
      recognizes numerous proinflammatory and anti-inflammatory stimuli, and emerging 
      reports indicate elevated levels of FPR2 in several disease conditions. Although 
      studies have implicated FPR2 in a myriad of inflammatory conditions, how viruses 
      exploit this cell-surface receptor to facilitate disease progression remains 
      unknown. In this study, we show that the activation of TLR3 and TLR7 induces the 
      up-regulation of FPR2. We provide evidence that signal transducer and activator 
      of transcription 3 (STAT3) phosphorylation is critical for the induction of FPR2 
      by double-stranded RNA, but not single-stranded RNA viral mimetics. Use of bone 
      marrow-derived macrophages (BMDMs) from IFN-alphabeta receptor-deficient mice revealed 
      that signaling via the type I IFN-STAT3 pathway is essential for FPR2 induction. 
      We demonstrate that virus infection with enterovirus 71 and H1N1 PR8 influenza 
      virus results in increased FPR2 expression. Inhibition of STAT3 phosphorylation 
      in virus-infected cells repressed the induction of FPR2, which led to a reduction 
      in viral loads. Finally, the absence of FPR2 in murine BMDMs resulted in lower 
      viral loads, which suggests that FPR2 may be important for virus replication. 
      Altogether, our study provides novel insights into how RNA viruses may hijack the 
      immune system to facilitate their replication and survival. Identification of 
      these regulatory elements may be useful in designing therapeutics for 
      inflammatory disease conditions that are associated with elevated levels of 
      FPR2.-Ampomah, P. B., Moraes, L. A., Lukman, H. M., Lim, L. H. K. Formyl peptide 
      receptor 2 is regulated by RNA mimics and viruses through an 
      IFN-beta-STAT3-dependent pathway.
FAU - Ampomah, Patrick B
AU  - Ampomah PB
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University 
      Health System.
AD  - Immunology Program, Life Sciences Institute, National University of Singapore, 
      Singapore.
FAU - Moraes, Leonardo A
AU  - Moraes LA
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University 
      Health System.
AD  - Immunology Program, Life Sciences Institute, National University of Singapore, 
      Singapore.
FAU - Lukman, Hakim M
AU  - Lukman HM
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University 
      Health System.
AD  - Immunology Program, Life Sciences Institute, National University of Singapore, 
      Singapore.
FAU - Lim, Lina H K
AU  - Lim LHK
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University 
      Health System.
AD  - Immunology Program, Life Sciences Institute, National University of Singapore, 
      Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180103
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Viral)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (TLR3 protein, mouse)
RN  - 0 (Tlr7 protein, mouse)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (formyl peptide receptor 2, mouse)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Animals
MH  - Enterovirus A, Human/*immunology
MH  - Enterovirus Infections/genetics/*immunology
MH  - Influenza A Virus, H1N1 Subtype/genetics/*immunology
MH  - Interferon-beta/genetics/immunology
MH  - Membrane Glycoproteins/genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Orthomyxoviridae Infections/genetics/*immunology
MH  - RNA, Viral/genetics/*immunology
MH  - Receptors, Formyl Peptide/genetics/*immunology
MH  - STAT3 Transcription Factor/genetics/*immunology
MH  - Signal Transduction/genetics/*immunology
MH  - Toll-Like Receptor 3/genetics/immunology
MH  - Toll-Like Receptor 7/genetics/immunology
OTO - NOTNLM
OT  - FPR2
OT  - IFN signaling
OT  - IRF3
OT  - innate immunity
EDAT- 2017/11/12 06:00
MHDA- 2018/11/07 06:00
CRDT- 2017/11/12 06:00
PHST- 2017/11/12 06:00 [pubmed]
PHST- 2018/11/07 06:00 [medline]
PHST- 2017/11/12 06:00 [entrez]
AID - fj.201700584RR [pii]
AID - 10.1096/fj.201700584RR [doi]
PST - ppublish
SO  - FASEB J. 2018 Mar;32(3):1468-1478. doi: 10.1096/fj.201700584RR. Epub 2018 Jan 3.