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Alteration of proteoglycan synthesis in human lung fibroblasts induced by interleukin-1beta and tumor necrosis factor-alpha

Tufvesson, Ellen LU and Westergren-Thorsson, Gunilla LU (2000) In Journal of Cellular Biochemistry 77(2). p.298-309
Abstract
Important constituents of extracellular matrix are collagen, fibronectin, hyaluronan, and various types of proteoglycans, such as versican, perlecan, decorin, and biglycan. Remodeling of extracellular matrix occurs continuously and is affected by various cytokines. The aim of this study was to investigate how interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), separately and in combination, alter fibroblast proliferation, as well as the production of extracellular matrix molecules produced by human fibroblasts from lung. Fibroblast proliferation was inhibited significantly by all treatments, by 12% with IL-1beta and by 16% with TNF-alpha. The combination of IL-1beta and TNF-alpha increased the inhibition further, by... (More)
Important constituents of extracellular matrix are collagen, fibronectin, hyaluronan, and various types of proteoglycans, such as versican, perlecan, decorin, and biglycan. Remodeling of extracellular matrix occurs continuously and is affected by various cytokines. The aim of this study was to investigate how interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), separately and in combination, alter fibroblast proliferation, as well as the production of extracellular matrix molecules produced by human fibroblasts from lung. Fibroblast proliferation was inhibited significantly by all treatments, by 12% with IL-1beta and by 16% with TNF-alpha. The combination of IL-1beta and TNF-alpha increased the inhibition further, by 27%. Hyaluronan production was increased by all treatments: 1.7-fold by IL-1beta and 1.5-fold by TNF-alpha. The combination of the two gave a further increase (2.5-fold). Similarly, the production of total proteoglycans was increased. The small proteoglycans, decorin, and biglycan, were regulated differently. Decorin production was inhibited by about 34% by all treatments, while biglycan was upregulated 1.3-fold by TNF-alpha. Versican was upregulated by IL-1beta (1.7-fold), whereas TNF-alpha was without effect. Perlecan was mostly unaffected. The changes in protein production of the various proteoglycans were due to increased transcription, as mRNA levels were also changed to the same extent. Synthesis of mRNA for collagen type I was inhibited by up to 75% with the IL-1beta/TNF-alpha combination. The separate cytokines also decreased the level of collagen type I mRNA, but to a lesser extent: 60% with IL-1beta and 40% with TNF-alpha. In summary, our study indicates that these proinflammatory cytokines affect the regulation of extracellular matrix production, which is of importance for the inflammatory process. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cellular Biochemistry
volume
77
issue
2
pages
298 - 309
publisher
Wiley-Blackwell
external identifiers
  • pmid:10723095
  • scopus:0034077130
ISSN
0730-2312
DOI
10.1002/(SICI)1097-4644(20000501)77:2<298::AID-JCB12>3.0.CO;2-D
language
English
LU publication?
yes
id
8a9c978f-a987-4c6c-9940-e6d7168d902f (old id 1117712)
date added to LUP
2008-06-26 15:55:20
date last changed
2017-10-22 03:44:14
@article{8a9c978f-a987-4c6c-9940-e6d7168d902f,
  abstract     = {Important constituents of extracellular matrix are collagen, fibronectin, hyaluronan, and various types of proteoglycans, such as versican, perlecan, decorin, and biglycan. Remodeling of extracellular matrix occurs continuously and is affected by various cytokines. The aim of this study was to investigate how interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), separately and in combination, alter fibroblast proliferation, as well as the production of extracellular matrix molecules produced by human fibroblasts from lung. Fibroblast proliferation was inhibited significantly by all treatments, by 12% with IL-1beta and by 16% with TNF-alpha. The combination of IL-1beta and TNF-alpha increased the inhibition further, by 27%. Hyaluronan production was increased by all treatments: 1.7-fold by IL-1beta and 1.5-fold by TNF-alpha. The combination of the two gave a further increase (2.5-fold). Similarly, the production of total proteoglycans was increased. The small proteoglycans, decorin, and biglycan, were regulated differently. Decorin production was inhibited by about 34% by all treatments, while biglycan was upregulated 1.3-fold by TNF-alpha. Versican was upregulated by IL-1beta (1.7-fold), whereas TNF-alpha was without effect. Perlecan was mostly unaffected. The changes in protein production of the various proteoglycans were due to increased transcription, as mRNA levels were also changed to the same extent. Synthesis of mRNA for collagen type I was inhibited by up to 75% with the IL-1beta/TNF-alpha combination. The separate cytokines also decreased the level of collagen type I mRNA, but to a lesser extent: 60% with IL-1beta and 40% with TNF-alpha. In summary, our study indicates that these proinflammatory cytokines affect the regulation of extracellular matrix production, which is of importance for the inflammatory process.},
  author       = {Tufvesson, Ellen and Westergren-Thorsson, Gunilla},
  issn         = {0730-2312},
  language     = {eng},
  number       = {2},
  pages        = {298--309},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Cellular Biochemistry},
  title        = {Alteration of proteoglycan synthesis in human lung fibroblasts induced by interleukin-1beta and tumor necrosis factor-alpha},
  url          = {http://dx.doi.org/10.1002/(SICI)1097-4644(20000501)77:2<298::AID-JCB12>3.0.CO;2-D},
  volume       = {77},
  year         = {2000},
}