PMID- 32173627
OWN - NLM
STAT- MEDLINE
DCOM- 20210729
LR  - 20210729
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 28
IP  - 5
DP  - 2020 May
TI  - Activation of innate immunity by 14-3-3 epsilon, a new potential alarmin in 
      osteoarthritis.
PG  - 646-657
LID - S1063-4584(20)30916-X [pii]
LID - 10.1016/j.joca.2020.03.002 [doi]
AB  - OBJECTIVE: The innate immune system plays a central role in osteoarthritis (OA). 
      We identified 14-3-3epsilon as a novel mediator that guides chondrocytes toward an 
      inflammatory phenotype. 14-3-3epsilon shares common characteristics with alarmins. 
      These endogenous molecules, released into extracellular media, are increasingly 
      incriminated in sustaining OA inflammation. Alarmins bind mainly to toll-like 
      receptor 2 (TLR2) and TLR4 receptors and polarize macrophages in the synovium. We 
      investigated the effects of 14-3-3epsilon in joint cells and tissues and its 
      interactions with TLRs to define it as a new alarmin involved in OA. DESIGN: 
      Chondrocyte, synoviocyte and macrophage cultures from murine or OA human samples 
      were treated with 14-3-3epsilon. To inhibit TLR2/4 in chondrocytes, blocking antibodies 
      were used. Moreover, chondrocytes and bone marrow macrophage (BMM) cultures from 
      knockout (KO) TLRs mice were stimulated with 14-3-3epsilon. Gene expression and release 
      of inflammatory mediators [interleukin 6 (IL-6), monocyte chemoattractant 
      protein-1 (MCP-1), tumor necrosis factor alpha (TNFalpha)] were evaluated via reverse 
      transcription quantitative polymerase chain reaction (RT-qPCR) and ELISA. 
      RESULTS: In vitro, 14-3-3epsilon induced gene expression and release of IL6 and MCP1 in 
      the treated cells. The inflammatory effects of 14-3-3epsilon were significantly reduced 
      following TLRs inhibition or in TLRs KO chondrocytes and BMM. CONCLUSIONS: 
      14-3-3epsilon is able to induce an inflammatory phenotype in synoviocytes, macrophages 
      and chondrocytes in addition to polarizing macrophages. These effects seem to 
      involve TLR2 or TLR4 to trigger innate immunity. Our results designate 14-3-3epsilon as 
      a novel alarmin in OA and as a new target either for therapeutic and/or 
      prognostic purposes.
CI  - Copyright (c) 2020 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Millerand, M
AU  - Millerand M
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France.
FAU - Sudre, L
AU  - Sudre L
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France.
FAU - Nefla, M
AU  - Nefla M
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France.
FAU - Pene, F
AU  - Pene F
AD  - Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France; Universite Paris 
      Descartes, Sorbonne Paris Cite, Paris France.
FAU - Rousseau, C
AU  - Rousseau C
AD  - Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France; Universite Paris 
      Descartes, Sorbonne Paris Cite, Paris France.
FAU - Pons, A
AU  - Pons A
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France.
FAU - Ravat, A
AU  - Ravat A
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France.
FAU - Andre-Leroux, G
AU  - Andre-Leroux G
AD  - MaIAGE, INRA, Universite Paris-Saclay, 78350 Jouy-en-Josas, France.
FAU - Akira, S
AU  - Akira S
AD  - Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), 
      Osaka University, Osaka 565-0871, Japan.
FAU - Satoh, T
AU  - Satoh T
AD  - Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), 
      Osaka University, Osaka 565-0871, Japan.
FAU - Berenbaum, F
AU  - Berenbaum F
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France; 
      Sorbonne Universite, Department of Rheumatology, AP-HP, Hopital Saint-Antoine, 
      and Labex Transimmunom, Paris, France. Electronic address: 
      francis.berenbaum@sat.aphp.fr.
FAU - Jacques, C
AU  - Jacques C
AD  - Sorbonne Universite, INSERM (UMR_S938) and Labex Transimmunom, Paris, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200312
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Alarmins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (YWHAE protein, human)
RN  - 0 (Ywhae protein, mouse)
SB  - IM
MH  - 14-3-3 Proteins/*immunology/pharmacology
MH  - Alarmins/immunology
MH  - Animals
MH  - Cartilage, Articular
MH  - Chemokine CCL2/genetics/immunology
MH  - Chondrocytes/drug effects/*immunology
MH  - Gene Expression
MH  - Humans
MH  - Immunity, Innate/drug effects/*immunology
MH  - In Vitro Techniques
MH  - Interleukin-6/genetics/immunology
MH  - Macrophages/drug effects/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Osteoarthritis, Knee/*immunology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Synovial Membrane
MH  - Synoviocytes/drug effects/*immunology
MH  - THP-1 Cells
MH  - Toll-Like Receptor 2/genetics
MH  - Toll-Like Receptor 4/genetics
MH  - Tumor Necrosis Factor-alpha/genetics/immunology
OTO - NOTNLM
OT  - 14-3-3 epsilon
OT  - Alarmin
OT  - Innate immunity
OT  - Osteoarthritis
OT  - Synovitis
OT  - TLR
EDAT- 2020/03/17 06:00
MHDA- 2021/07/30 06:00
CRDT- 2020/03/17 06:00
PHST- 2019/06/20 00:00 [received]
PHST- 2020/02/24 00:00 [revised]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/03/17 06:00 [pubmed]
PHST- 2021/07/30 06:00 [medline]
PHST- 2020/03/17 06:00 [entrez]
AID - S1063-4584(20)30916-X [pii]
AID - 10.1016/j.joca.2020.03.002 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2020 May;28(5):646-657. doi: 
      10.1016/j.joca.2020.03.002. Epub 2020 Mar 12.