Depending on environmental influences, follicular outer root sheath (ORS) cells in vivo can differentiate either towards interfollicular keratinocytes or, as demonstrated in the rat vibrissa, hair matrix cells. Crucial regulators of both their proliferation and differentiation are the mesenchymal cells of the respective tissues. The interactions of human ORS cells with human hair papilla cells (HPC) or human dermal fibroblasts (HDF) were studied using a two-chamber model separating the two cell types either by a microporous membrane or additionally by a medium layer. The results of 3H-thymidine incorporation studies indicated that ORS cell growth was markedly enhanced in co-culture with either HPC or HDF, the highest stimulatory effect resulting when ORS cells were in close association with the mesenchymal cells. No correlation was found between ORS cell proliferation and IL-6 production in the co-culture system, thus pointing to the secretion by HPC and HDF of growth-promoting soluble factors that are different form IL-6 as well as from EGF, bFGF and insulin present in the culture medium.

Soluble cytokine receptors appear to modify ligand concentrations by stabilizing ligands or by specifically inhibiting interactions of ligands with their membrane-bound receptors. Here we describe a new function of the soluble interleukin-1 receptor type I (IL-1sR I). This receptor induced a transient rise of intracellular free calcium concentration in human dermal fibroblasts in a dose-dependent fashion. Mobilization of calcium by IL-1sR I was abolished in the presence of an equimolar concentration of IL-1 receptor antagonist (IL-1ra). Neutralizing antibodies against IL-1L L also abolished calcium mobilization stimulated with IL-1sR I indicating that IL-1L L is involved. IL1sR I bound with high affinity (K d 1^2 nM) to the fibroblasts. In addition, IL-1sR I enhanced expression of IL-6 and IL-8 mRNA. The observation that IL-1sR I can act as a ligand and agonist for membrane IL-1 extends the concept of the ligand-receptor functions of both IL-1 and IL-1sR I and adds a new dimension to the cytokine network.z 1998 Federation of European Biochemical Societies.

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To obtain additional information on the in vivo injury induced by PUVA treatment, primary cultures were initiated from biopsies of the uninvolved skin of 15 PUVA-treated psoriatic patients, and the cells generated were analysed for morphological and chromosomal modifications. Three biopsies were obtained from each patient, the first one before commencing PUVA therapy (control) and the other two during the course of therapy. It was found that PUVA treatment has diverse effects on the mitotic activity, mitotic mechanisms and chromosomes of the cutaneous cells: (1) an inhibition of cell proliferation during the early stages of therapy followed by a reversion to normal proliferation as the PUVA treatments were continued; the production of (2) cells with more than one nucleus, (3) macrocells, (4) cells with micronuclei, (5) polyploid cells, (6) haploid cells, (7) cells with 13 chromosomes denoting a twofold reduction in the normal number of metaphase chromosomes, (8) end-associations of the chromosomes as in the pachytene phase of meiosis (9) diplotene chromosomes, and (10) chromosomal translocations.