TNF-alpha induces the transcription factor Egr-1, pro-inflammatory cytokines and cell proliferation in human skin fibroblasts and synovial lining cells.
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.
Grimbacher
B
B
Clinical Research Unit for Rheumatology, University of Freiburg, Medical School, Germany.
Aicher
W K
WK
Peter
H H
HH
Eibel
H
H
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*
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