Original Article

Journal of Investigative Dermatology (1994) 102, 118–121; doi:10.1111/1523-1747.ep12371743

Inhibition of Collagen Lattice Contraction by Pentoxifylline and Interferon-Alpha, -Beta and -Gamma

Michael J Dans and Rivkah Isseroff

Department of Dermatology, University of California, Davis, California, U.S.A.

Received 29 June 1993; Accepted 13 September 1993.

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Abstract

The ability to control wound contraction is important in preventing disfiguring scarring in burn and trauma patients. Fibroblasts within the wound generate the mechanical forces that cause this contraction, and their interactions with various extracellular matrix components are thought to regulate this process. Because pentoxifylline and the interferons are believed to moderate fibroblast production of such matrix components, we assessed the effects of these agents on wound contraction in vitro, using a model wherein dermal fibroblasts are incorporated into a collagen lattice. Pentoxifylline and interferon-alpha, -beta, and -gamma inhibited lattice contraction in a dose-dependent manner and showed no effect on cell number or cell viability. These results suggest that pentoxifylline and the interferons may retard wound contraction in vivo and thus reduce scarring associated with severely contracted wounds. Further study is needed to determine the mechanism of action of these agents on the collagen lattice model.

Keywords:

collagen lattice, wound healing, pentoxifylline, interferon, dermal equivalent

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References

  1. Bell, E, Sher, S, Hull, B, Merrill, C, Rosen, S, Chamson, A, Asselineau, D, Dubertret, L, Coulomb, B, Lapiere, C, Nusgens, B, Neveux, Y: The reconstitution of living skin. J Invest Dermatol 81: 2S–10S, 1983 | Article | PubMed | ChemPort |
  2. Elsdale, T, Bard, J: Collagen substrata for studies on cell behaviour. J Cell Biol 54: 626–639, 1972 | Article | PubMed | ISI | ChemPort |
  3. Tomasek, JJ, Hay, ED, Fujiwara, K: Collagen modulates cell shape and cytoskeleton of embryonic corneal and fibroma fibroblasts: distribution of actin, alphaactinin, and myosin. Dev Biol 92: 107–122, 1982 | PubMed | ISI | ChemPort |
  4. Bell, E, Ivarsson, B, Merrill, C: Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci USA 76: 1274–1278, 1979 | PubMed | ChemPort |
  5. Duncan, MR, Berman, B: Differential regulation of glycosaminoglycan, fibronectin, and collagenase production in cultured human dermal fibroblasts by interferon-alpha, -beta, and -gamma. Arch Dermatol Res 281: 11–18, 1989
  6. Gillery, P, Serpier, H, Polette, M, Bellon, G, Clavel, C, Wegrowski, Y, Birembaut, P, Kalis, B, Cariou, R, Maquart, F: Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts. Eur J Cell Biol 57: 244–253, 1992
  7. Montesano, R, Orci, L: Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci USA 85: 4894–4897, 1988 | PubMed | ChemPort |
  8. Clark, RAF, Folkvord, JM, Hart, CE, Murray, MJ, McPherson, JM: Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices. J Clin Invest 84: 1036–1040, 1989 | PubMed | ISI | ChemPort |
  9. Rittenberg, T, Burd, DAR, Ehrlich, HP: Soluble factor(s) in rat wound fluid inhibit fibroblast populated lattice contraction. Exp Mol Pathol 52: 132–140, 1990
  10. Burd, DAR, Longaker, MT, Rittenberg, T, Adzick, NS, Harrison, MR, Ehrlich, HP: In vitro foetal wound contraction: the effect of amniotic fluid. Br J Plastic Surg 44: 302–305, 1991
  11. Adams, LW, Priestley, GC: Contraction of collagen lattices by skin fibroblasts: drug-induced changes. Arch Dermatol Res 280: 114–118, 1988
  12. Ward, RS: Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. J Burn Care Rehab 12: 257–262, 1991
  13. Olbrisch, RR: Running Y-V plasty. Ann Plastic Surg 26: 52–56, 1991
  14. Mooney, MP, Siegel, MI, Hurwitz, DJ, Edington, H: Pharmacologic manipulation of postoperative labial wound contraction and midfacial growth in rabbits. Plastic Reconstructive Surg 88: 121–128, 1991
  15. Busca, GP, Amasio, ME, Sartoris, A: Complications of rhinoplasty. Acta Otorhinolarygolo Ital 10: 1–37, 1990
  16. Fang, CH, Alexander, JW: Wound contraction following transplantation of microskin autografts with overlaid skin allograft in experimental animals. Burns 16: 190–192, 1990
  17. Guidry, C, Grinnell, F: Heparin modulates the organization of hydrated collagen gels and inhibits gel contraction by fibroblasts. J Cell Biol 104: 1097–1103, 1987
  18. Docherty, R, Forrester, JV, Lackie, JM, Gregory, DW: Glycosaminoglycans facilitate the movement of fibroblasts through three-dimensional collagen matrices. J Cell Sci 92: 263–270, 1989
  19. Asaga, H, Kikuchi, S, Yoshizato, K: Collagen gel contraction by fibroblasts requires cellular fibronectin but not plasma fibronectin. Exp Cell Res 193: 167–174, 1991
  20. Gullberg, D, Terracio, L, Borg, TK, Rubin, K: Identification of integrin-like matrix receptors with affinity for interstitial collagens. J Biol Chem 264: 12686–12694, 1989
  21. Tomasek, JJ, Akiyama, SK: Fibroblast-mediated collagen gel contraction does not require fibronectin-alpha 5 beta 1 integrin interaction. Anatomical Rec 234: 153–160, 1992
  22. Ehrly, AM, Saiger-Lorenz, K: Increased capillary flow rate of erythrocytes in hyperosmolar human blood by the addition of pentoxifylline. In: Grayson J, Zingg W (eds.). Microcirculation 1: Plenum Press, New York, pp 165–166, 1976
  23. Ely, H: Pentoxifylline therapy in dermatology: a review of localized hyperviscosity and its effects on the skin. Dermatol Clin 6: 585–607, 1988
  24. Berman, B, Duncan, MR: Pentoxifylline inhibits normal human dermal fibroblast in vitro proliferation, collagen, glycosaminoglycan, and fibronectin production, and increases collagenase activity. J Invest Dermatol 92: 605–610, 1989
  25. Isseroff, R, Ziboh, VA, Chapkin, RS, Martinez, DT: Conversion of linoleic acid into arachidonic acid by murine and human keratinocytes. J Lipid Res 28: 1342–1349, 1987 | PubMed | ISI | ChemPort |
  26. Berman, B, Duncan, MR: Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. Br J Dermatol 123: 339–346, 1990
  27. Pestka, S, Langer, JA, Zoon, KC, Samuel, CE: Interferons and their actions. Annu Rev Biochem 56: 727–777, 1987 | Article | PubMed | ISI | ChemPort |
  28. Nakagawa, S, Pawelek, P, Grinnell, F: Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness. Expr Cell Res 182: 572–582, 1989
  29. Nishiyama, T, Horii, I, Nakayama, Y, Ozawa, T, Hayashi, T: A distinct characteristic of the quiescent state of human dermal fibroblasts in contracted collagen gel as revealed by no response to epidermal growth factor alone, but a positive growth response to a combination of the growth factor and saikosponin B 1. Matrix 10: 412–419, 1990
  30. Buttle, DJ, Ehrlich, HP: Comparative studies of collagen lattice contraction utilizing a normal and a transformed cell line. J Cell Physiol 116: 159–166, 1983
  31. Martin, P, Hopkinson-Woolley, J, McCluskey, J: Growth factors and cutaneous wound repair. Progr Growth Factor Res 4: 25–44, 1992
  32. Clark, RAF: Growth factors and wound repair. J Cell Biochem 46: 1–2, 1991

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