PMID- 14734750
OWN - NLM
STAT- MEDLINE
DCOM- 20040507
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 172
IP  - 3
DP  - 2004 Feb 1
TI  - Hypoxia selectively inhibits monocyte chemoattractant protein-1 production by 
      macrophages.
PG  - 1681-90
AB  - Hypoxia, a local decrease in oxygen tension occurring in inflammatory and tumor 
      lesions, modulates gene expression in macrophages. Because macrophages are 
      important chemokine producers, we investigated the regulatory effects of hypoxia 
      on macrophage-derived chemokines. We demonstrated that hypoxia inhibits the 
      production of the macrophage and T lymphocyte chemotactic and activating factor, 
      monocyte chemoattractant protein-1 (MCP-1). Exposure of mouse macrophages to low 
      oxygen tension resulted in the down-regulation of constitutive MCP-1 mRNA 
      expression and protein secretion. Hypoxia inhibitory effects were selective for 
      MCP-1 because the chemokines macrophage inflammatory protein-1beta (MIP-1beta), 
      RANTES, IFN-gamma-inducible protein-10, and MIP-2 were not affected, and 
      MIP-1alpha was induced. Hypoxia also inhibited, in a time-dependent fashion, 
      MCP-1 up-regulation by IFN-gamma and LPS. Moreover, the inhibitory action of 
      hypoxia was exerted on human monocytic cells. MCP-1 down-regulation was 
      associated with inhibition of gene transcription and mRNA destabilization, 
      suggesting a dual molecular mechanism of control. Finally, we found that the 
      triptophan catabolite picolinic acid and the iron chelator desferrioxamine, which 
      mimic hypoxia in the induction of gene expression, differentially regulated the 
      expression of MCP-1. This study characterizes a novel property of hypoxia as a 
      selective inhibitor of MCP-1 production induced by different stimuli in 
      macrophages and demonstrates that down-regulation of gene expression by hypoxia 
      can be controlled at both transcriptional and posttranscriptional levels. 
      Inhibition of MCP-1 may represent a negative regulatory mechanism to control 
      macrophage-mediated leukocyte recruitment in pathological tissues.
FAU - Bosco, Maria Carla
AU  - Bosco MC
AD  - Laboratory of Molecular Biology, G. Gaslini Institute, Genova, Italy. 
      mcbosco1@virgilio.it
FAU - Puppo, Maura
AU  - Puppo M
FAU - Pastorino, Sandra
AU  - Pastorino S
FAU - Mi, Zenghui
AU  - Mi Z
FAU - Melillo, Giovanni
AU  - Melillo G
FAU - Massazza, Stefano
AU  - Massazza S
FAU - Rapisarda, Annamaria
AU  - Rapisarda A
FAU - Varesio, Luigi
AU  - Varesio L
LA  - eng
GR  - N01-CO-56000/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Picolinic Acids)
RN  - 0 (RNA, Messenger)
RN  - 82115-62-6 (Interferon-gamma)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - QZV2W997JQ (picolinic acid)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/drug effects/immunology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/*antagonists & inhibitors/*biosynthesis/genetics
MH  - Deferoxamine/pharmacology
MH  - Down-Regulation/drug effects/*immunology
MH  - Gene Expression Regulation/drug effects/immunology
MH  - Humans
MH  - Interferon-gamma/antagonists & inhibitors/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophage Activation/immunology
MH  - Macrophages/drug effects/*immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxygen/metabolism
MH  - Picolinic Acids/pharmacology
MH  - RNA Stability/immunology
MH  - RNA, Messenger/metabolism
MH  - Transcription, Genetic/immunology
EDAT- 2004/01/22 05:00
MHDA- 2004/05/08 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/05/08 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
AID - 10.4049/jimmunol.172.3.1681 [doi]
PST - ppublish
SO  - J Immunol. 2004 Feb 1;172(3):1681-90. doi: 10.4049/jimmunol.172.3.1681.