Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease which results in end-stage fibrosis. The pathogenesis is believed to be related to a dysregulation in cross-talk between inflammatory and structural cells, mediated by various cytokines, chemokines and growth factors, which are responsible for the maintenance of tissue homeostasis and which coordinate the response to injury. The large number of mediators involved and the complexity of their interaction makes it difficult to identify the factors responsible for initiation of fibrogenesis and progression to chronicity. Whether a mediator ’ s presence in fibrotic lung is as a result of tissue injury or if it playsan active role in disease onset and progression has been partly answered by the use of transient and / or permanent transgenic and gene knock-out approaches to over-express single factors at a time. Chemokines such as interleukin-8 (IL-8), RANTES, IP-10, MIG or lymphotactin, do not appear to induce fibrosis when over-expressed in rodent lung. Amongst many tested, four cytokines and growth factors have been found to be pro-fibrotic; IL-1β, which demonstrates marked inflammation, tissue damage and chronic fibrosis, TNF-?, which induces inflammation and mild fibrosis, and GM-CSF, which induces moderate inflammation and fibrosis. A common finding with these cytokines are increased lung TGF-β levels, proportionate to the degree of fibrosis generated, while TGF-β itself causes minor inflammation but marked progressive chronic fibrosis. A growth factor ‘downstream’ from the pro-fibrotic effects of TGF-β, CTGF, is a likely critical mediator. However, over-expression of CTGF produces only mild and reversible fibrosis.
Keywords: Fibrogenic Cytokines, cytokines, RANTES, lymphotactin, homeostasis
Current Pharmaceutical Design
Title: Re-evaluation of Fibrogenic Cytokines in Lung Fibrosis
Volume: 9 Issue: 1
Author(s): Margaret Kelly, Martin Kolb, Phillipe Bonniaud and Jack Gauldie
Affiliation:
Keywords: Fibrogenic Cytokines, cytokines, RANTES, lymphotactin, homeostasis
Abstract: Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease which results in end-stage fibrosis. The pathogenesis is believed to be related to a dysregulation in cross-talk between inflammatory and structural cells, mediated by various cytokines, chemokines and growth factors, which are responsible for the maintenance of tissue homeostasis and which coordinate the response to injury. The large number of mediators involved and the complexity of their interaction makes it difficult to identify the factors responsible for initiation of fibrogenesis and progression to chronicity. Whether a mediator ’ s presence in fibrotic lung is as a result of tissue injury or if it playsan active role in disease onset and progression has been partly answered by the use of transient and / or permanent transgenic and gene knock-out approaches to over-express single factors at a time. Chemokines such as interleukin-8 (IL-8), RANTES, IP-10, MIG or lymphotactin, do not appear to induce fibrosis when over-expressed in rodent lung. Amongst many tested, four cytokines and growth factors have been found to be pro-fibrotic; IL-1β, which demonstrates marked inflammation, tissue damage and chronic fibrosis, TNF-?, which induces inflammation and mild fibrosis, and GM-CSF, which induces moderate inflammation and fibrosis. A common finding with these cytokines are increased lung TGF-β levels, proportionate to the degree of fibrosis generated, while TGF-β itself causes minor inflammation but marked progressive chronic fibrosis. A growth factor ‘downstream’ from the pro-fibrotic effects of TGF-β, CTGF, is a likely critical mediator. However, over-expression of CTGF produces only mild and reversible fibrosis.
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Cite this article as:
Kelly Margaret, Kolb Martin, Bonniaud Phillipe and Gauldie Jack, Re-evaluation of Fibrogenic Cytokines in Lung Fibrosis, Current Pharmaceutical Design 2003; 9 (1) . https://dx.doi.org/10.2174/1381612033392341
DOI https://dx.doi.org/10.2174/1381612033392341 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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