PMID- 21338623
OWN - NLM
STAT- MEDLINE
DCOM- 20110801
LR  - 20110415
IS  - 1879-0542 (Electronic)
IS  - 0165-2478 (Linking)
VI  - 137
IP  - 1-2
DP  - 2011 Jun 30
TI  - IFN-gamma directly inhibits TNF-alpha-induced osteoclastogenesis in vitro and in vivo and 
      induces apoptosis mediated by Fas/Fas ligand interactions.
PG  - 53-61
LID - 10.1016/j.imlet.2011.02.017 [doi]
AB  - Cytokines secreted by T cells play a pivotal role in inflammatory bone 
      destruction. Tumor necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine 
      produced by macrophages following T cell activation, and directly promotes 
      osteoclast differentiation resulting in accelerated bone resorption. Interferon-gamma 
      (IFN-gamma) attenuates RANKL-initiated cellular signals through osteoclast formation 
      and counterbalances aberrant bone resorption. With respect to this crosstalk 
      during osteoclastogenesis, the direct interruption of IFN-gamma in TNF-alpha-induced 
      osteoclast formation still requires elucidation. We have demonstrated that IFN-gamma 
      directly inhibits osteoclastogenesis induced by TNF-alpha stimulation and accelerates 
      apoptosis mediated by Fas/Fas ligand signals. There were a decreased number of 
      osteoclasts and reduced mRNA levels encoding Nfatc1 in cultured bone marrow 
      macrophages. Apoptotic responses of cultured cells were observed, with 
      accelerated nuclear fragmentation in osteoclast precursor cells and increased 
      FasL mRNA levels in bone marrow cells stimulated with TNF-alpha evident. IFN-gamma 
      reduced the level of osteoclastogenesis in response to TNF-alpha treatment in vivo. 
      IFN-gamma inhibited TNF-alpha-induced osteoclastogenesis in mice with T cells that had 
      been exposed to anti-CD4 and -CD8 antibodies. These results provide evidence that 
      IFN-gamma directly inhibits osteoclastogenesis and induces cells apoptosis by 
      Fas/FasL signals, leading to the indirect regulation of bone resorption, which is 
      required for protective roles in bone destruction at an inflammation site.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Kohara, Haruka
AU  - Kohara H
AD  - Department of Orthodontics and Dentofacial Orthopedics, Nagasaki University 
      Graduate School of Biomedical Sciences, Japan. dm07002h@cc.nagasaki-u.ac.jp
FAU - Kitaura, Hideki
AU  - Kitaura H
FAU - Fujimura, Yuji
AU  - Fujimura Y
FAU - Yoshimatsu, Masako
AU  - Yoshimatsu M
FAU - Morita, Yukiko
AU  - Morita Y
FAU - Eguchi, Toshiko
AU  - Eguchi T
FAU - Masuyama, Ritsuko
AU  - Masuyama R
FAU - Yoshida, Noriaki
AU  - Yoshida N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110219
PL  - Netherlands
TA  - Immunol Lett
JT  - Immunology letters
JID - 7910006
RN  - 0 (Fas Ligand Protein)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Bone Resorption/genetics/*immunology/prevention & control
MH  - Cells, Cultured
MH  - Fas Ligand Protein/genetics/*metabolism
MH  - Interferon-gamma/*pharmacology
MH  - Macrophages/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - NFATC Transcription Factors/genetics/metabolism
MH  - Osteoclasts/drug effects/immunology/*metabolism/pathology
MH  - Osteogenesis Imperfecta/genetics/*immunology/prevention & control
MH  - RNA, Messenger/analysis
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2011/02/23 06:00
MHDA- 2011/08/02 06:00
CRDT- 2011/02/23 06:00
PHST- 2010/11/02 00:00 [received]
PHST- 2011/02/03 00:00 [revised]
PHST- 2011/02/14 00:00 [accepted]
PHST- 2011/02/23 06:00 [entrez]
PHST- 2011/02/23 06:00 [pubmed]
PHST- 2011/08/02 06:00 [medline]
AID - S0165-2478(11)00057-5 [pii]
AID - 10.1016/j.imlet.2011.02.017 [doi]
PST - ppublish
SO  - Immunol Lett. 2011 Jun 30;137(1-2):53-61. doi: 10.1016/j.imlet.2011.02.017. Epub 
      2011 Feb 19.