PMID- 11167995 OWN - NLM STAT- MEDLINE DCOM- 20010308 LR - 20220410 IS - 0009-9104 (Print) IS - 1365-2249 (Electronic) IS - 0009-9104 (Linking) VI - 123 IP - 1 DP - 2001 Jan TI - Hypoxia induces expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and IL-8 in human dermal fibroblasts. PG - 36-41 AB - 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. FAU - Galindo, M AU - Galindo M AD - Unidad de Investigacion, Hospital 12 de Octubre, Madrid, Spain. reuma@h12o.es FAU - Santiago, B AU - Santiago B FAU - Alcami, J AU - Alcami J FAU - Rivero, M AU - Rivero M FAU - Martin-Serrano, J AU - Martin-Serrano J FAU - Pablos, J L AU - Pablos JL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-8) RN - 0 (NF-kappa B) RN - S88TT14065 (Oxygen) SB - IM MH - Cell Hypoxia/*immunology MH - Cell Line MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/metabolism/physiology MH - Chemotaxis, Leukocyte/immunology MH - Fibroblasts/*immunology/metabolism MH - Humans MH - Interleukin-8/*biosynthesis MH - Monocytes/immunology MH - NF-kappa B/metabolism MH - Oxygen/metabolism MH - Skin/cytology/*immunology/metabolism PMC - PMC1905951 EDAT- 2001/02/13 11:00 MHDA- 2001/03/10 10:01 PMCR- 2002/01/01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/03/10 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] PHST- 2002/01/01 00:00 [pmc-release] AID - cei1412 [pii] AID - 10.1046/j.1365-2249.2001.01412.x [doi] PST - ppublish SO - Clin Exp Immunol. 2001 Jan;123(1):36-41. doi: 10.1046/j.1365-2249.2001.01412.x.