Hypoxia induces expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and IL-8 in human dermal fibroblasts.
Hypoxia is an important factor in the pathophysiology of vascular and inflammatory diseases. Leucocyte infiltration, as a consequence of adhesion molecule up-regulation and chemokine release, is a prominent feature of these diseases. The objective of our study was to investigate the potential role of resident fibroblasts in hypoxia-induced chemotactic responses. We show that MCP-1 and IL-8 mRNA are specifically induced by hypoxia in dermal fibroblasts. This response is paralleled by increased NF-kappaB p65/p50 binding activity, and it is inhibited by pretreatment with N-acetyl-L-cysteine. MCP-1 secreted by fibroblasts is chemotactic for monocytic cells and this activity is significantly increased by hypoxia. Chemotactic index correlates with MCP-1 protein levels and is significantly decreased by neutralizing anti-MCP-1 MoAb. These findings demonstrate the ability of resident fibroblasts to mediate chemotaxis of leucocytes through the release of chemokines in response to hypoxia. Our data point to MCP-1 as an important component in this response, and therefore it may be a potential target in inflammatory responses associated with hypoxia.
Galindo
M
M
Unidad de Investigación, Hospital 12 de Octubre, Madrid, Spain. reuma@h12o.es
Santiago
B
B
Alcami
J
J
Rivero
M
M
Martín-Serrano
J
J
Pablos
J L
JL
D015687:Cell Hypoxia / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D010100:Oxygen