Characterization of alpha-enolase as an interferon-alpha 2 alpha 1 regulated gene.
Interferons (IFNs) are multifunctional cytokines that after binding to the cell surface receptor induce the expression of a large number of genes, which in turn, mediate many biological processes including host defense, cell growth control, signaling, and metabolism. Here we show that IFN-alpha activates the mitogen-activated protein kinases (MAPK) ERK1/2 and the transcription factor CREB/ATF-1, which lead to the alpha-enolase (alpha-ENO) gene expression in fibroblasts. Alpha-ENO mRNA accumulation was apparent 6 h post-IFN stimulation and required both de novo protein synthesis and active gene transcription, which is typical of a secondary response gene. Alpha-ENO expression does not appear to be restricted to fibroblasts, since it was equally verified in peripheral blood mononuclear cells (PBMC). Furthermore, IFN-alpha stimulates the expression of the primary response genes c-fos and egr-1, which was followed by an increase in DNA binding activity of c-FOS and EGR-1 proteins, as verified by shift assays using the cis-acting elements AP-1 and EGR-1 localized at the alpha-ENO promoter. Finally, we also demonstrated that IFN treatment of PBMC cause an increase in both, alpha-ENO expression on the cell surface and plasmin generation followed addition of exogenous plasminogen.
Sousa
Lirlândia P
LP
Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Brasil
Bruno S A F
BS
Silva
Breno De M
Bde M
Nogueira
Sarah V
SV
Andrade
Anderson A
AA
Ferreira
Paulo C P
PC
Teixeira
Santuza M R
SM
Gollob
Kenneth J
KJ
Kroon
Erna G
EG
Kato
Kanefusa
K
Bonjardim
Cláudio A
CA
D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015854:Up-Regulation
D017362:Cyclic AMP Response Element-Binding Protein; D016898:Interferon-alpha; D007371:Interferon-gamma; D048052:Mitogen-Activated Protein Kinase 3; D005341:Fibrinolysin; D010751:Phosphopyruvate Hydratase