Ets-1 Regulates TNF-α-Induced Matrix Metalloproteinase-9 and Tenascin Expression in Primary Bronchial Fibroblasts

Yutaka Nakamura, Stéphane Esnault, Takashi Maeda, Elizabeth A B Kelly, James S. Malter, Nizar N. Jarjour

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Increased subepithelial deposition of extracellular matrix proteins is a key feature in bronchial asthma. Matrix metalloproteinase-9 (MMP-9) is a proteolytic enzyme that degrades the extracellular matrix. Tenascin is an extracellular matrix glycoprotein that is abundant in thickened asthmatic subbasement membrane. The expression of MMP-9 and tenascin reflects disease activity in asthma and airway remodeling. The molecular mechanisms regulating the expression of these proteins remain unknown. Both MMP-9 and tenascin promoters contain an Ets binding site, suggesting control by Ets-1. Thus, we hypothesized that Ets-1 expression is increased in asthma and that it contributed to enhanced MMP-9 and tenascin expression. To test this hypothesis, we determined the expression of Ets-1 in bronchial biopsies obtained from asthmatic subjects and determined the expression of Ets-1, MMP-9, and tenascin by bronchial fibroblasts activated ex vivo. We observed that nuclear extracts from TNF-α-activated fibroblasts showed increased Ets-binding activity. In addition, TNF-α-activated fibroblasts had increased expression of Ets-1 mRNA and protein, which preceded an increase in MMP-9 and tenascin mRNA. Furthermore, treatment of fibroblasts with Ets-1 antisense oligonucleotides down-regulated TNF-α-induced Ets-1, MMP-9, and, to a lesser extent, tenascin protein expression or activity. Taken together, these data demonstrate that TNF-α increases MMP-9 and tenascin expression in bronchial fibroblasts via the transcription factor Ets-1, and suggest a role for Ets-1 in airway remodeling in asthma.

Original languageEnglish (US)
Pages (from-to)1945-1952
Number of pages8
JournalJournal of Immunology
Volume172
Issue number3
StatePublished - Feb 1 2004

Fingerprint

Tenascin
Matrix Metalloproteinase 9
Fibroblasts
Asthma
Airway Remodeling
Extracellular Matrix
Proto-Oncogene Protein c-ets-1
Messenger RNA
Proteins
Antisense Oligonucleotides
Extracellular Matrix Proteins
Glycoproteins
Peptide Hydrolases
Binding Sites
Biopsy
Membranes

ASJC Scopus subject areas

  • Immunology

Cite this

Nakamura, Y., Esnault, S., Maeda, T., Kelly, E. A. B., Malter, J. S., & Jarjour, N. N. (2004). Ets-1 Regulates TNF-α-Induced Matrix Metalloproteinase-9 and Tenascin Expression in Primary Bronchial Fibroblasts. Journal of Immunology, 172(3), 1945-1952.

Ets-1 Regulates TNF-α-Induced Matrix Metalloproteinase-9 and Tenascin Expression in Primary Bronchial Fibroblasts. / Nakamura, Yutaka; Esnault, Stéphane; Maeda, Takashi; Kelly, Elizabeth A B; Malter, James S.; Jarjour, Nizar N.

In: Journal of Immunology, Vol. 172, No. 3, 01.02.2004, p. 1945-1952.

Research output: Contribution to journalArticle

Nakamura, Y, Esnault, S, Maeda, T, Kelly, EAB, Malter, JS & Jarjour, NN 2004, 'Ets-1 Regulates TNF-α-Induced Matrix Metalloproteinase-9 and Tenascin Expression in Primary Bronchial Fibroblasts', Journal of Immunology, vol. 172, no. 3, pp. 1945-1952.
Nakamura, Yutaka ; Esnault, Stéphane ; Maeda, Takashi ; Kelly, Elizabeth A B ; Malter, James S. ; Jarjour, Nizar N. / Ets-1 Regulates TNF-α-Induced Matrix Metalloproteinase-9 and Tenascin Expression in Primary Bronchial Fibroblasts. In: Journal of Immunology. 2004 ; Vol. 172, No. 3. pp. 1945-1952.
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