PMID- 10586089
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20081121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 12
DP  - 1999 Dec 15
TI  - Activation of eotaxin gene transcription by NF-kappa B and STAT6 in human airway 
      epithelial cells.
PG  - 6876-83
AB  - The C-C chemokine eotaxin is a potent chemoattractant for eosinophils and
      probably plays an important role in the pathogenesis of asthma, although the
      mechanisms of its regulation are not well known. Airway epithelial cells express 
      eotaxin mRNA and protein after stimulation with a variety of cytokines. We
      focused on the molecular mechanisms of eotaxin gene regulation by TNF-alpha and
      IL-4 in the airway epithelial cell line, BEAS-2B. Cells were transfected with
      luciferase reporter plasmids, which contained up to 1363 bp of the eotaxin
      promoter. Eotaxin promoter activity was increased by TNF-alpha (2.5-fold) and
      IL-4 (1.5-fold), respectively. The combination of TNF-alpha and IL-4 produced
      3.6-fold activation of the eotaxin promoter. The eotaxin promoter contains
      overlapping consensus binding sites for transcription factors, NF-kappa B and
      STAT6, which are known to mediate responses to TNF-alpha and IL-4, respectively. 
      Electrophoretic mobility shift assays revealed NF-kappa B binding after TNF-alpha
      stimulation and STAT6 binding after IL-4 stimulation using a DNA probe derived
      from the eotaxin promoter. Mutant plasmids were generated to define the roles of 
      these transcription factors in eotaxin promoter activity. TNF-alpha stimulation, 
      but not IL-4 stimulation, was lost in plasmids mutated at the NF-kappa B binding 
      site, whereas IL-4 stimulation, but not TNF-alpha stimulation, was lost in
      plasmids mutated at the STAT6 binding site. When both sites were mutated, all
      transcriptional activation was lost. These results imply that TNF-alpha and IL-4 
      stimulate expression of the eotaxin gene by activating NF-kappa B and STAT6.
FAU - Matsukura, S
AU  - Matsukura S
AD  - Division of Clinical Immunology and Allergy, Johns Hopkins Asthma and Allergy
      Center, Baltimore, MD 21224, USA.
FAU - Stellato, C
AU  - Stellato C
FAU - Plitt, J R
AU  - Plitt JR
FAU - Bickel, C
AU  - Bickel C
FAU - Miura, K
AU  - Miura K
FAU - Georas, S N
AU  - Georas SN
FAU - Casolaro, V
AU  - Casolaro V
FAU - Schleimer, R P
AU  - Schleimer RP
LA  - eng
GR  - AI44885/AI/NIAID NIH HHS/United States
GR  - R01AR31891/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CCL11 protein, human)
RN  - 0 (Chemokine CCL11)
RN  - 0 (Chemokines, CC)
RN  - 0 (Chemotactic Factors, Eosinophil)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - AIM
SB  - IM
MH  - Base Sequence
MH  - Binding Sites/genetics/immunology
MH  - Blotting, Western
MH  - Bronchi/cytology/immunology/*metabolism
MH  - Cell Line
MH  - Chemokine CCL11
MH  - *Chemokines, CC
MH  - Chemotactic Factors, Eosinophil/*genetics/isolation & purification
MH  - Cloning, Molecular
MH  - Cytokines/*genetics/isolation & purification
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Epithelial Cells/immunology/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism/*physiology
MH  - Promoter Regions, Genetic
MH  - STAT6 Transcription Factor
MH  - Signal Transduction/*genetics/immunology
MH  - Trans-Activators/metabolism/*physiology
MH  - Transcriptional Activation/drug effects/*immunology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - ji_v163n12p6876 [pii]
PST - ppublish
SO  - J Immunol. 1999 Dec 15;163(12):6876-83.