Interleukin-1-induced growth factor expression in postmitotic and resting fibroblasts.
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.
Maas-Szabowski
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Division of Differentiation and Carcinogenesis, German Cancer Research Center, Heidelberg.
Fusenig
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NE
D000328:Adult; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases