Differential regulation of interleukin-8 and intercellular adhesion molecule-1 by H2O2 and tumor necrosis factor-alpha in endothelial and epithelial cells.
J Biol Chem
; 272(52): 32910-8, 1997 Dec 26.
Article
em En
| MEDLINE
| ID: mdl-9407069
ABSTRACT
The reactive oxygen intermediate H2O2 can function as a signaling molecule to activate gene expression. In this study, we demonstrate that oxidant stress induced by tumor necrosis factor alpha (TNFalpha) or H2O2 differentially regulates intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) gene expression in endothelial and epithelial cells. Northern blot analysis revealed that TNFalpha induced both ICAM-1 and IL-8 expression in either the A549 lung epithelial cell line or the human microvessel endothelial cell line (HMEC-1). In contrast, H2O2 selectively induced only ICAM-1 in HMEC-1 and only IL-8 in A549. This cell type-specific pattern of IL-8 expression was also observed in several other endothelial and epithelial cells. TNFalpha induced greater IL-8 gene expression as compared with H2O2, but the kinetics of induction were similar. The induction of epithelial IL-8 message was accompanied by a corresponding increase in functional IL-8 protein secretion as determined by a neutrophil motility assay. The increased neutrophil motility stimulated by conditioned media from H2O2- or TNFalpha-exposed A549 cells was completely inhibited by an anti-IL-8 antibody. TNFalpha and H2O2 also induced a differential pattern of CC chemokine expression in A549. While TNFalpha induced both RANTES and MCP-1, H2O2 induced only MCP-1. These data suggest that epithelial cells under oxidant stress contribute to the inflammatory cytokine network by selective production of IL-8, MCP-1, and RANTES, which may critically influence the site-specific recruitment of leukocyte subsets.
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Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Interleucina-8
/
Fator de Necrose Tumoral alfa
/
Molécula 1 de Adesão Intercelular
/
Células Epiteliais
/
Peróxido de Hidrogênio
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article