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.
Silverman
Eric S
ES
Division of Pulmonary and Critical Care Medicine and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston 02115, USA. esilverm@hsph.harvard.edu
Baron
Rebecca M
RM
Palmer
Lyle J
LJ
Le
Louis
L
Hallock
Arlene
A
Subramaniam
Venkat
V
Riese
Richard J
RJ
McKenna
Matthew D
MD
Gu
Xuesong
X
Libermann
Towia A
TA
Tugores
Antonio
A
Haley
Kathleen J
KJ
Shore
Stephanie
S
Drazen
Jeffrey M
JM
Weiss
Scott T
ST
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C403306:EHF protein, human; C116038:ELF5 protein, human; D007375:Interleukin-1; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1