Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung.
Family studies of asthma suggest that the genes ESE-2 and ESE-3 contain polymorphisms that contribute to disease susceptibility. Each gene codes for an ETS transcription factor that is characterized by epithelium-restricted constitutive expression and may function as a context-dependent activator or repressor of transcription; however, nothing is known about the role of these genes in lung homeostasis or the pathogenesis of airway disease. In this study, we show that ESE-3 mRNA and protein are constitutively expressed in bronchial and mucous gland epithelial cells. Consistent with these findings, ESE-3 mRNA is constitutively expressed in human bronchial epithelial cells grown in tissue culture. In contrast, ESE-2 mRNA could not be detected in the lung or cultured human bronchial epithelial cells. Human bronchial smooth muscle cells and fibroblasts do not constitutively express ESE-3; however, after stimulation with interleukin-1beta or tumor necrosis factor-alpha, levels of ESE-3 mRNA and protein increase dramatically by 24 h. This cytokine induction is dose-dependent and abrogated by specific inhibitors of the MEK1/2 (U0126) and p38 (SB03580) signal transduction pathways. Overexpression of ESE-3 protein in 3T3 cells and human bronchial smooth muscle cells inhibits MMP-1 promoter activity, suggesting that ESE-3 may function as a transcriptional repressor.
Published In/Presented At
Silverman, E. S., Baron, R. M., Palmer, L. J., Le, L., Hallock, A., Subramaniam, V., Riese, R. J., McKenna, M. D., Gu, X., Libermann, T. A., Tugores, A., Haley, K. J., Shore, S., Drazen, J. M., & Weiss, S. T. (2002). Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung. American journal of respiratory cell and molecular biology, 27(6), 697–704. https://doi.org/10.1165/rcmb.2002-0011OC
Medicine and Health Sciences
Department of Medicine