PMID- 11922866
OWN - NLM
STAT- MEDLINE
DCOM- 20021202
LR  - 20191105
IS  - 1471-2334 (Electronic)
IS  - 1471-2334 (Linking)
VI  - 2
DP  - 2002 Mar 28
TI  - Respiratory syncytial virus and TNF alpha induction of chemokine gene expression 
      involves differential activation of Rel A and NF-kappa B1.
PG  - 5
AB  - 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.
FAU - Carpenter, Laura R
AU  - Carpenter LR
AD  - Department of Immunology/Microbiology, Rush-Presbyterian-St, Luke's Medical 
      Center Chicago, IL 60612, USA. lcarpent@rush.edu
FAU - Moy, James N
AU  - Moy JN
FAU - Roebuck, Kenneth A
AU  - Roebuck KA
LA  - eng
GR  - AR45835/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020328
PL  - England
TA  - BMC Infect Dis
JT  - BMC infectious diseases
JID - 100968551
RN  - 0 (Antiviral Agents)
RN  - 0 (Chemokines)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Glucocorticoids)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Antiviral Agents/pharmacology
MH  - Chemokines/biosynthesis/*genetics
MH  - Dexamethasone/pharmacology
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects/*physiology
MH  - Glucocorticoids/pharmacology
MH  - Humans
MH  - Lung Neoplasms/genetics/metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism/*physiology
MH  - Oxidation-Reduction
MH  - Respiratory Syncytial Viruses/drug effects/isolation & purification/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism/*physiology
PMC - PMC102322
EDAT- 2002/04/02 10:00
MHDA- 2002/12/03 04:00
PMCR- 2002/03/28
CRDT- 2002/04/02 10:00
PHST- 2001/08/28 00:00 [received]
PHST- 2002/03/28 00:00 [accepted]
PHST- 2002/04/02 10:00 [pubmed]
PHST- 2002/12/03 04:00 [medline]
PHST- 2002/04/02 10:00 [entrez]
PHST- 2002/03/28 00:00 [pmc-release]
AID - 1471-2334-2-5 [pii]
AID - 10.1186/1471-2334-2-5 [doi]
PST - epublish
SO  - BMC Infect Dis. 2002 Mar 28;2:5. doi: 10.1186/1471-2334-2-5.