© 2002 American Thoracic Society DOI: 10.1165/rcmb.2002-0011OC Constitutive and Cytokine-Induced Expression of the ETS Transcription Factor ESE-3 in the LungDivision of Pulmonary and Critical Care Medicine and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston; New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center, Boston; Harvard Medical School, Boston; Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio; and Parc Cientific Barcelona, Barcelona, Spain Address correspondence to: Eric S. Silverman, M.D., Department of Environmental Health, Harvard School of Public Health, 667 Huntington Ave., Boston, MA 02115. E-mail: esilverm{at}hsph.harvard.edu
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-1ß or tumor necrosis factor-
Abbreviations: Ets binding site, EBS • epithelium-specific expression, ESE • interleukin, IL • human bronchial epithelial cells, HBEC • human bronchial fibroblasts, HBFB • human bronchial smooth muscle cells, HBSMC • mitogen-activated protein kinase, MAPK • matrix metalloproteinase, MMP • phosphate-buffered saline, PBS • tumor necrosis factor, TNF This article has been cited by other articles:
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, 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. 
