Alteration of proteoglycan synthesis in human lung fibroblasts induced by interleukin-1beta and tumor necrosis factor-alpha
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1117712
- author
- Tufvesson, Ellen LU and Westergren-Thorsson, Gunilla LU
- organization
- publishing date
- 2000
- 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
- 2016-04-01 12:02:46
- date last changed
- 2024-06-18 06:38:43
@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}}, doi = {{10.1002/(SICI)1097-4644(20000501)77:2<298::AID-JCB12>3.0.CO;2-D}}, volume = {{77}}, year = {{2000}}, }