Expression of cytokines and their receptors by psoriatic fibroblasts. II. decreased TNF receptor expression.
Psoriatic fibroblasts produce enhanced amounts of IL-6 in vitro. This state of activation may reflect an altered expression of cytokine receptors, involved in auto/paracrine induction of IL-6. Cultures of dermal fibroblasts derived from lesional psoriatic (PP) and normal control (NN) skin were therefore analysed for their ability to bind biotinylated recombinant human cytokines using flow cytometry. PP and NN fibroblasts bound negligible amounts of IL-1 alpha and IL-1 beta, but clearly bound IL-4, IL-6 and TNF-alpha. Serum upregulated the number of NN fibroblasts which bound TNF-alpha, and to a lesser extent IL-6, but not the number of binding sites per cell. In contrast, this upregulation was significantly less in PP fibroblasts. This was not a result of differences in growth characteristics, receptor occupancy or an inability of stimulated PP fibroblasts to bind TNF-alpha. Immunocytochemistry of cells grown on slides showed that the TNF receptor type 1 (TNFR1, p55) was the predominant receptor in NN fibroblasts and was localized to the nucleus of cytoplasma. The expression of TNFR1 was clearly decreased in PP fibroblasts, which confirmed the binding studies. A slow and serum-induced shedding of TNFR1 was observed, but not of the TNFR2 (p75), in both types of fibroblasts. Confluent multi-passaged PP fibroblasts display both a decreased TNFR expression as well as an enhanced IL-6 production under serum conditions. These inherent abnormalities of PP fibroblasts imply the involvement of dermal fibroblasts in the maintenance of chronic inflammation in psoriasis.
Debets
R
R
Department of Immunology, Erasmus University Rotterdam, Netherlands.
Hegmans
J P
JP
Buurman
W A
WA
Benner
R
R
Prens
E P
EP
D002118:Calcium / Q000494:pharmacology; D002453:Cell Cycle; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*; D018121:Receptors, Cytokine / Q000032:analysis / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D012016:Reference Values; D012867:Skin / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D018121:Receptors, Cytokine; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium