The transcription factor early growth-response factor 1 modulates tumor necrosis factor-alpha, immunoglobulin E, and airway responsiveness in mice.
Early growth-response factor 1 (Egr-1) is a sequence-specific transcription factor that plays a regulatory role in the expression of many genes important in inflammation, cell growth, apoptosis, and the pathogenesis of disease. In vitro studies suggest that Egr-1 is capable of regulating the expression of tumor necrosis factor-alpha (TNF-alpha) and other genes involved in airway inflammation and reactivity following allergen stimulation. On the basis of these data, we hypothesized that in the absence of Egr-1, the TNF-alpha response and subsequent downstream inflammatory events that usually follow allergen challenge would be diminished. To test our hypothesis Egr-1 knock-out (KO) mice were examined in an ovalbumin (OVA)-induced model of airway inflammation and reactivity, and compared with identically treated wild-type (WT) control mice. In response to OVA sensitization and airway challenge, KO mice had diminished TNF-alpha mRNA and protein in the lungs and mast cells compared with WT mice. Interestingly, the KO mice had elevated IgE levels at baseline and after allergen challenge compared with WT mice. Furthermore, the airways of KO mice were hyporesponsive to methacholine challenge at baseline and after allergen challenge. These data indicate that Egr-1 modulates TNF-alpha, IgE, and airway responsiveness in mice.
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. esilverm@rics.bwh.harvard.edu
E S
ES
Silverman
G T
GT
De Sanctis
J
J
Boyce
J A
JA
Maclean
A
A
Jiao
F H
FH
Green
H
H
Grasemann
D
D
Faunce
G
G
Fitzmaurice
G P
GP
Shi
J
J
Stein-Streilein
J
J
Milbrandt
T
T
Collins
J M
JM
Drazen
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins / Q000502:physiology*; D007073:Immunoglobulin E / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E