Expression of cytokines and their receptors by psoriatic fibroblast. I. Altered IL-6 synthesis.
Interleukin(IL-)6 is overproduced in psoriatic lesions. We investigated the contribution of dermal fibroblasts to the local IL-6 production. Fibroblasts (passageno. 2 to 6) derived from lesional psoriatic (PP) and normal human (NN) skin were used to analyse the secretion of IL-6, and the related cytokines IL-1, IL-8 and TNF-alpha, and the expression of their corresponding mRNA by bioassay, ELISA and Northern hybridization, respectively. PP fibroblasts cultured under serum-free conditions produced increased amounts of bioactive IL-6 when compared to NN fibroblasts. Differences were partially restored in the presence of growth factors or serum. The serum-induced IL-6 production reached a maximum within 24 h after seeding and remained unchanged in PP fibroblasts, whereas comparable amounts of IL-6 were produced only 6 days later in NN fibroblasts. There was a clear expression of IL-6 mRNA in both types of fibroblasts under serum-free conditions. Unexpectedly, fetal calf serum, inactivated fetal calf serum as well as human serum completely inhibited the expression of IL-6 mRNA in all the PP fibroblast cultures investigated. NN fibroblasts were clearly less sensitive to this inhibiting effect of serum. Furthermore, medium supplemented with serum-free component or calcium also repressed IL-6 mRNA expression in PP fibroblasts in contrast to NN fibroblasts. Cycloheximide fully restored the repressing effect of serum indicating that serum induced a labile repressor protein. PP and NN fibroblasts produced negligible amounts of IL-1 and TNF-alpha, but the production of IL-8, however, was comparable to that of IL-6. Our results show a differently regulated IL-6 synthesis in PP fibroblasts in vitro, suggesting an active contribution of dermal fibroblasts to the local IL-6 production in psoriasis.
Debets
R
R
Department of Immunology, Erasmus University Rotterdam, Netherlands.
Hegmans
J P
JP
Deleuran
M
M
Hooft
S
S
Benner
R
R
Prens
E P
EP
D015152:Blotting, Northern; D002478:Cells, Cultured; D003470:Culture Media; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis; D007700:Kinetics; D011565:Psoriasis / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D012016:Reference Values; D012867:Skin / Q000276:immunology*; D013997:Time Factors
D003470:Culture Media; D017077:Culture Media, Conditioned; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D018121:Receptors, Cytokine