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 import ant in inflammation, cell growth, apoptosis, and the pathogenesis of diseas e. In vitro studies suggest that Egr-1 is capable of regulating the express ion of tumor necrosis factor-alpha (TNF-alpha) and other genes involved in airway inflammation and reactivity following allergen stimulation. On the b asis of these data, we hypothesized that in the absence of Egr-1, the TNF-a lpha response and subsequent downstream inflammatory events that usually fo llow allergen challenge would be diminished. To test our hypothesis Egr-1 k nock-out (KO) mice were examined in an ovalbumin (OVA)-induced model of air way inflammation and reactivity, and compared with identically treated wild -type (WT) control mice. In response to OVA sensitization and airway challe nge, KO mice had diminished TNF-alpha mRNA and protein in the lungs and mas t cells compared with WT mice. Interestingly, the KO mice had elevated IgE levels at baseline and after allergen challenge compared with WT mice. Furt hermore, the airways of KO mice were hyporespon sive to methacholine challe nge at baseline and after allergen challenge. These data indicate that Egr- 1 modulates TNF-alpha, IgE, and airway responsiveness in mice.