Interleukin-1-induced growth factor expression in postmitotic and resting fibroblasts

J Invest Dermatol. 1996 Dec;107(6):849-55. doi: 10.1111/1523-1747.ep12331158.


Tissue homeostasis in skin is regulated by epithelial-mesenchymal interactions, mostly operating via diffusible factors. To study the underlying regulatory mechanisms, in vitro systems have been established to mimic the in vivo situation in skin. In co-cultures, keratinocytes grow either adjacent to irradiated fibroblasts on plastic or on top of collagen gels containing fibroblasts, thus forming 3-dimensional organotypic structures. Keratinocyte growth is supported in part by fibroblast-produced factors induced by keratinocyte mediators such as interleukin-1 (IL-1). To better understand this cellular interaction and its modulation by fibroblast proliferation and extracellular matrix (ECM), we examined the effect of IL-1 on growth factor expression in proliferating and growth-arrested x-irradiated human dermal fibroblasts on plastic and in resting cells embedded in collagen gels. By semiquantitative reverse transcriptase PCR, we demonstrated that IL-1alpha and IL-1beta stimulated the expression of KGF, HGF, IL-1alpha, IL-1beta, IL-1RI, and IL-8 in fibroblasts regardless of their physiologic condition, whereas that of TGF-beta remained unaffected. The constitutive mRNA levels were usually lower in irradiated postmitotic and ECM-embedded cells than in proliferating fibroblasts. Cells responded to stimulation with IL-1 under all three culture conditions, although to different degrees depending on the growth factor. As demonstrated for HGF, IL-8, and IL-1beta, the IL-1alpha-induced mRNA expression was followed by production and secretion of protein in irradiated fibroblasts. Thus, our findings show that resting and growth-inhibited fibroblasts, reflecting more closely the situation in dermis, exhibit lower constitutive growth factor expression levels but characteristically respond to IL-1 stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Communication
  • Cell Division / drug effects
  • Cells, Cultured
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Growth Substances / metabolism*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-1 / pharmacology*
  • Interleukin-8 / metabolism
  • Keratinocytes / cytology
  • RNA, Messenger / metabolism
  • Time Factors


  • FGF7 protein, human
  • Fibroblast Growth Factor 10
  • Growth Substances
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Hepatocyte Growth Factor
  • Glyceraldehyde-3-Phosphate Dehydrogenases