PMID- 25088998
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20201209
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 451
IP  - 2
DP  - 2014 Aug 22
TI  - IL-27 affects helper T cell responses via regulation of PGE2 production by 
      macrophages.
PG  - 215-21
LID - S0006-291X(14)01345-X [pii]
LID - 10.1016/j.bbrc.2014.07.096 [doi]
AB  - IL-27 is a heterodimeric cytokine that regulates both innate and adaptive 
      immunity. The immunosuppressive effect of IL-27 largely depends on induction of 
      IL-10-producing Tr1 cells. To date, however, effects of IL-27 on regulation of 
      immune responses via mediators other than cytokines remain poorly understood. To 
      address this issue, we examined immunoregulatory effects of conditional medium of 
      bone marrow-derived macrophages (BMDMs) from WSX-1 (IL-27Ralpha)-deficient mice and 
      found enhanced IFN-gamma and IL-17A secretion by CD4(+) T cells as compared with that 
      of control BMDMs. We then found that PGE2 production and COX-2 expression by 
      BMDMs from WSX-1-deficient mice was increased compared to control macrophages in 
      response to LPS. The enhanced production of IFN-gamma and IL-17A was abolished by EP2 
      and EP4 antagonists, demonstrating PGE2 was responsible for enhanced cytokine 
      production. Murine WSX-1-expressing Raw264.7 cells (mWSX-1-Raw264.7) showed 
      phosphorylation of both STAT1 and STAT3 in response to IL-27 and produced less 
      amounts of PGE2 and COX-2 compared to parental RAW264.7 cells. STAT1 knockdown in 
      parental RAW264.7 cells and STAT1-deficiency in BMDMs showed higher COX-2 
      expression than their respective control cells. Collectively, our result 
      indicated that IL-27/WSX-1 regulated PGE2 secretion via STAT1-COX-2 pathway in 
      macrophages and affected helper T cell response in a PGE2-mediated fashion.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Sato, Yayoi
AU  - Sato Y
AD  - Dept. of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 
      849-8501, Japan; Dept. of Molecular & Cellular Biology, Kobe Pharma Research 
      Institute, Nippon Boehringer Ingelheim Co., Ltd., Kobe 650-0047, Japan; Lab 
      Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita 
      565-0871, Japan.
FAU - Hara, Hiromitsu
AU  - Hara H
AD  - Dept. of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 
      849-8501, Japan.
FAU - Okuno, Toshiaki
AU  - Okuno T
AD  - Dept. of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, 
      Japan.
FAU - Ozaki, Naoko
AU  - Ozaki N
AD  - Dept. of Molecular & Cellular Biology, Kobe Pharma Research Institute, Nippon 
      Boehringer Ingelheim Co., Ltd., Kobe 650-0047, Japan.
FAU - Suzuki, Shinobu
AU  - Suzuki S
AD  - Dept. of Molecular & Cellular Biology, Kobe Pharma Research Institute, Nippon 
      Boehringer Ingelheim Co., Ltd., Kobe 650-0047, Japan.
FAU - Yokomizo, Takehiko
AU  - Yokomizo T
AD  - Dept. of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, 
      Japan.
FAU - Kaisho, Tsuneyasu
AU  - Kaisho T
AD  - Lab Immune Regulation, Immunology Frontier Research Center, Osaka University, 
      Suita 565-0871, Japan.
FAU - Yoshida, Hiroki
AU  - Yoshida H
AD  - Dept. of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 
      849-8501, Japan. Electronic address: yoshidah@med.saga-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140801
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Il27 protein, mouse)
RN  - 0 (Il27ra protein, mouse)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, Cytokine)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Culture Media, Conditioned
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/*biosynthesis
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-17/biosynthesis
MH  - Interleukins/*metabolism
MH  - Macrophages/*immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, Cytokine/deficiency/genetics/metabolism
MH  - Receptors, Interleukin
MH  - STAT1 Transcription Factor/deficiency/genetics/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Helper-Inducer/*immunology/metabolism
OTO - NOTNLM
OT  - COX-2
OT  - Helper T cells
OT  - IL-27
OT  - Macrophage
OT  - Prostaglandin
EDAT- 2014/08/05 06:00
MHDA- 2014/10/22 06:00
CRDT- 2014/08/05 06:00
PHST- 2014/06/26 00:00 [received]
PHST- 2014/07/22 00:00 [accepted]
PHST- 2014/08/05 06:00 [entrez]
PHST- 2014/08/05 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
AID - S0006-291X(14)01345-X [pii]
AID - 10.1016/j.bbrc.2014.07.096 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2014 Aug 22;451(2):215-21. doi: 
      10.1016/j.bbrc.2014.07.096. Epub 2014 Aug 1.