Hypoxia induces expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and IL-8 in human dermal fibroblasts

Clin Exp Immunol. 2001 Jan;123(1):36-41. doi: 10.1046/j.1365-2249.2001.01412.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia / immunology*
  • Cell Line
  • Cells, Cultured
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL2 / physiology
  • Chemotaxis, Leukocyte / immunology
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-8 / biosynthesis*
  • Monocytes / immunology
  • NF-kappa B / metabolism
  • Oxygen / metabolism
  • Skin / cytology
  • Skin / immunology*
  • Skin / metabolism


  • Chemokine CCL2
  • Interleukin-8
  • NF-kappa B
  • Oxygen