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Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis
BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to mu...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762410/ https://www.ncbi.nlm.nih.gov/pubmed/17205112 http://dx.doi.org/10.1371/journal.pone.0000108 |
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author | Oikonomou, Nikos Harokopos, Vaggelis Zalevsky, Jonathan Valavanis, Christos Kotanidou, Anastasia Szymkowski, David E. Kollias, George Aidinis, Vassilis |
author_facet | Oikonomou, Nikos Harokopos, Vaggelis Zalevsky, Jonathan Valavanis, Christos Kotanidou, Anastasia Szymkowski, David E. Kollias, George Aidinis, Vassilis |
author_sort | Oikonomou, Nikos |
collection | PubMed |
description | BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis. |
format | Text |
id | pubmed-1762410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-17624102007-01-04 Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis Oikonomou, Nikos Harokopos, Vaggelis Zalevsky, Jonathan Valavanis, Christos Kotanidou, Anastasia Szymkowski, David E. Kollias, George Aidinis, Vassilis PLoS One Research Article BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis. Public Library of Science 2006-12-27 /pmc/articles/PMC1762410/ /pubmed/17205112 http://dx.doi.org/10.1371/journal.pone.0000108 Text en Oikonomou et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Oikonomou, Nikos Harokopos, Vaggelis Zalevsky, Jonathan Valavanis, Christos Kotanidou, Anastasia Szymkowski, David E. Kollias, George Aidinis, Vassilis Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis |
title | Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis |
title_full | Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis |
title_fullStr | Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis |
title_full_unstemmed | Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis |
title_short | Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis |
title_sort | soluble tnf mediates the transition from pulmonary inflammation to fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762410/ https://www.ncbi.nlm.nih.gov/pubmed/17205112 http://dx.doi.org/10.1371/journal.pone.0000108 |
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