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Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1

Tingström, Anders LU ; Heldin, Carl-Henrik and Rubin, Kristofer LU (1992) In Journal of Cell Science 102(2). p.315-322
Abstract
We have examined the effects of three macrophagederived

cytokines, platelet-derived growth factor (PDGF), transforming growth factor-01 (TGF-01) and interleukin-1 a (IL-la) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-/J1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF Lsoforms. However, the stimulatory effect of TGF-/S1 was not affected by any of the anti-PDGF... (More)
We have examined the effects of three macrophagederived

cytokines, platelet-derived growth factor (PDGF), transforming growth factor-01 (TGF-01) and interleukin-1 a (IL-la) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-/J1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF Lsoforms. However, the stimulatory effect of TGF-/S1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate

contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-/J1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF ^-receptor aggregates when compared to fibroblasts on attached collagen gels. LL-1 a inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-la and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone. At later stages, collagen gel degradation was stimulated by this combination of cytokines. In contrast, the combination

of IL-la and TGF-/51 did not stimulate collagen gel

contraction, or any visible collagen gel degradation. Our

data suggest that fibroblast-mediated collagen gel contraction can be modulated by cytokines via different

mechanisms. Our data are of importance in the understanding of the modulatory roles of cytokines in connective tissue cell activities in inflammatory processes, such as wound healing. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fibroblasts, transforming growth factor-^3, plateletderived growth factor, interleukin-1, collagen
in
Journal of Cell Science
volume
102
issue
2
pages
315 - 322
publisher
The Company of Biologists Ltd
external identifiers
  • pmid:1400635
ISSN
0021-9533
language
English
LU publication?
yes
id
670475bf-4e57-434c-8b84-a90686c712b0 (old id 1106830)
alternative location
http://jcs.biologists.org/cgi/reprint/102/2/315
date added to LUP
2008-08-12 09:50:44
date last changed
2016-04-15 19:54:42
@article{670475bf-4e57-434c-8b84-a90686c712b0,
  abstract     = {We have examined the effects of three macrophagederived<br/><br>
cytokines, platelet-derived growth factor (PDGF), transforming growth factor-01 (TGF-01) and interleukin-1 a (IL-la) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-/J1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF Lsoforms. However, the stimulatory effect of TGF-/S1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate<br/><br>
contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-/J1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF ^-receptor aggregates when compared to fibroblasts on attached collagen gels. LL-1 a inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-la and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone. At later stages, collagen gel degradation was stimulated by this combination of cytokines. In contrast, the combination<br/><br>
of IL-la and TGF-/51 did not stimulate collagen gel<br/><br>
contraction, or any visible collagen gel degradation. Our<br/><br>
data suggest that fibroblast-mediated collagen gel contraction can be modulated by cytokines via different<br/><br>
mechanisms. Our data are of importance in the understanding of the modulatory roles of cytokines in connective tissue cell activities in inflammatory processes, such as wound healing.},
  author       = {Tingström, Anders and Heldin, Carl-Henrik and Rubin, Kristofer},
  issn         = {0021-9533},
  keyword      = {fibroblasts,transforming growth factor-^3,plateletderived
growth factor,interleukin-1,collagen},
  language     = {eng},
  number       = {2},
  pages        = {315--322},
  publisher    = {The Company of Biologists Ltd},
  series       = {Journal of Cell Science},
  title        = {Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1},
  volume       = {102},
  year         = {1992},
}