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BMC Infect Dis. 2002 Mar 28;2:5.

Respiratory syncytial virus and TNF alpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappa B1.

Author information

1
Department of Immunology/Microbiology, Rush-Presbyterian-St, Luke's Medical Center Chicago, IL 60612, USA. lcarpent@rush.edu

Abstract

BACKGROUND:

Respiratory syncytial virus (RSV) infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated upon activation, normal T cell expressed and secreted). Chemokines are important chemoattractants for the recruitment of distinct sets of leukocytes to airway sites of inflammation.

RESULTS:

We have shown previously that chemokine expression is regulated in airway epithelial cells (A549) in a stimulus-specific manner in part through the redox-responsive transcription factors AP-1 and NF-kappaB. In this study, we examined the NF-kappaB-mediated effects of RSV and the proinflammatory cytokine TNFalpha on the induction of IL-8, MCP-1 and RANTES chemokine gene expression in A549 epithelial cells. The results demonstrate that RSV induces chemokine expression with distinct kinetics that is associated with a specific pattern of NF-kappaB binding activity. This distinction was further demonstrated by the differential effects of the NF-kappaB inhibitors dexamethasone (DEX) and N-acetyl-L-cysteine (NAC). NAC preferentially inhibited RSV induced chemokine expression, whereas DEX preferentially inhibited TNFalpha induced chemokine expression. DNA binding studies using NF-kappaB subunit specific binding ELISA demonstrated that RSV and TNFalpha induced different NF-kappaB binding complexes containing Rel A (p65) and NF-kappaB1 (p50). Both TNFalpha and RSV strongly induced Rel A the activation subunit of NF-kappaB, whereas only TNFalpha was able to substantially induce the p50 subunit. Consistent with the expression studies, RSV but not TNFalpha induction of Rel A and p50 were markedly inhibited by NAC, providing a mechanism by which TNFalpha and RSV can differentially activate chemokine gene expression via NF-kappaB.

CONCLUSIONS:

These data suggest that RSV induction of chemokine gene expression, in contrast to TNFalpha, involves redox-sensitive NF-kappaB complexes containing predominantly Rel A.

PMID:
11922866
PMCID:
PMC102322
[Indexed for MEDLINE]
Free PMC Article

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