Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-kappaB.

Abstract:

:The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines by the reactive oxidant H2O2, the proinflammatory cytokine TNF-alpha, and respiratory syncytial virus (RSV) is mediated in a cell type-specific manner involving different patterns of AP-1 and NF-kappaB binding activity. Our results demonstrate that H2O2 induction of IL-8 gene expression is linked with the selective binding of AP-1 to the IL-8 promoter, whereas TNF-alpha and RSV induction of IL-8 correlates with the activation of NF-kappaB binding. We propose that the differential activation and binding of inducible transcription factors to the promoter regions of chemokine genes provides a critical regulatory mechanism by which the CXC and CC chemokines can be selectively expressed in a cell type-specific and stimulus-specific manner. Such a regulatory mechanism of differential chemokine expression could critically influence the site-specific recruitment of distinct subsets of leukocytes to sites of inflammation and injury.

journal_name

J Leukoc Biol

authors

Roebuck KA,Carpenter LR,Lakshminarayanan V,Page SM,Moy JN,Thomas LL

doi

10.1002/jlb.65.3.291

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

291-8

issue

3

eissn

0741-5400

issn

1938-3673

journal_volume

65

pub_type

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