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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

fibroblasts

transforming growth factor-^3

plateletderived growth factor

interleukin-1

collagen

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