title: TNF-alpha induces the transcription factor Egr-1, pro-inflammatory cytokines and cell proliferation in human skin fibroblasts and synovial lining cells.
abstract: In rheumatoid arthritis (RA) cell proliferation and altered metalloproteinase expression of synovial lining cells are associated with increased levels of TNF-alpha in the rheumatoid joint. We previously showed that synoviocytes of RA patients express high levels of the transcription factor Egr-1. Here we report that TNF-alpha is capable of inducing high Egr-1 mRNA levels in human skin fibroblasts and in synoviocytes from both, RA and reactive arthritis patients. Moreover, we observed in vitro a marked increase in fibroblast proliferation, a loss of growth inhibition by cell-to-cell contact with pannus-like cell growth and an altered cytokine expression pattern when synoviocytes were cultured in presence of TNF-alpha.
authors.affiliation: Clinical Research Unit for Rheumatology, University of Freiburg, Medical School, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Grimbacher
authors.forename: W K
authors.initials: WK
authors.lastname: Aicher
authors.forename: H H
authors.initials: HH
authors.lastname: Peter
authors.forename: H
authors.initials: H
authors.lastname: Eibel
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics; D051766:Early Growth Response Protein 1; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins; D008297:Male; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013583:Synovial Membrane / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha