PMID- 12270755
OWN - NLM
STAT- MEDLINE
DCOM- 20021104
LR  - 20220321
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 71
IP  - 21
DP  - 2002 Oct 11
TI  - Interferon-gamma-induced apoptosis and activation of THP-1 macrophages.
PG  - 2499-508
AB  - Apoptotic macrophages are frequently observed in human atherosclerotic lesions, 
      and are considered to be involved in plaque instability in atherosclerosis. 
      However, the molecular mechanism that promotes programmed cell death of 
      macrophages in atherosclerosis remains to be elucidated. In this study, we 
      investigated the effects of interferon-gamma (IFN-gamma), a cytokine secreted by 
      activated T helper 1 (Th1) lymphocytes, on apoptotic cell death of THP-1 
      macrophages. Further we studied whether these apoptotic macrophages could be 
      simultaneously activated in vitro and subsequently overgenerate monocyte 
      chemoattractant protein-1 (MCP-1). When THP-1 macrophages were cultured with 
      various concentrations of IFN-gamma, DNA synthesis was significantly decreased. 
      IFN-gamma was found significantly to induce apoptotic cell death in THP-1 
      macrophages. RNase protection assay revealed that IFN-gamma up-regulated the mRNA 
      levels of two pro-apoptotic molecules, tumor necrosis factor-alpha receptor 1 
      (TNFR1) and caspase-8, in THP-1 cells. Furthermore, TNF-alpha antibodies were 
      found completely to neutralize the IFN-gamma-induced inhibition in DNA synthesis 
      as well as apoptotic cell death in macrophages. IFN-gamma was found to activate 
      these macrophages to stimulate MCP-1 production. The results suggest that 
      IFN-gamma not only exerted apoptotic effects on macrophages, but also activated 
      them and subsequently overgenerated MCP-1, and was thus involved in the 
      development and progression of atherosclerosis.
FAU - Inagaki, Yosuke
AU  - Inagaki Y
AD  - Department of Medicine, Division of Endocrinology and Metabolism, Kurume 
      University School of Medicine, Japan.
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
FAU - Amano, Shinjiro
AU  - Amano S
FAU - Okamoto, Tamami
AU  - Okamoto T
FAU - Koga, Kohachiro
AU  - Koga K
FAU - Makita, Zenji
AU  - Makita Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antigens, CD)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antibodies, Blocking/pharmacology
MH  - Antigens, CD/genetics/metabolism
MH  - Apoptosis/*drug effects
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/genetics/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Interferon-gamma/immunology/*pharmacology
MH  - Macrophage Activation/*drug effects
MH  - Macrophages/*drug effects/immunology/pathology
MH  - Neutralization Tests
MH  - RNA, Messenger/metabolism
MH  - Receptors, Tumor Necrosis Factor/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Th1 Cells/drug effects/metabolism
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/immunology
EDAT- 2002/09/25 06:00
MHDA- 2002/11/26 04:00
CRDT- 2002/09/25 06:00
PHST- 2002/09/25 06:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/09/25 06:00 [entrez]
AID - S0024320502020428 [pii]
AID - 10.1016/s0024-3205(02)02042-8 [doi]
PST - ppublish
SO  - Life Sci. 2002 Oct 11;71(21):2499-508. doi: 10.1016/s0024-3205(02)02042-8.