Regulation of GRB2 and FLICE2 expression by TNF-alpha in rheumatoid synovium.
Chronic rheumatoid arthritis (RA) is characterized by the hyperplasia of synovial tissue, which results from dysregulation of proliferative and antiapoptotic signals transduced in the synovial cells by unknown mechanisms. To identify candidate factors involved in the regulation of synovial hyperplasia, the expression profile of 205 apoptosis-related genes was compared between tissues from patients with RA and osteoarthritis (OA) using a cDNA microarray. Upregulated genes in the RA synovium included TNFR2, FLICE2, and signaling molecules involved in a MAP kinase pathway (GRB2, MAPK p38). In contrast, genes encoding SARP1 and various cell cycle regulators were down-regulated in the RA synovium relative to OA. Importantly, the expression levels of GRB2 and FLICE2 genes were remarkably enhanced in RA synoviocytes but not in OA synoviocytes in response to tumor necrosis factor (TNF)-alpha treatment. Thus, these results suggest that over-expression of GRB2 and FLICE2 in RA synovium is caused by TNF-alpha inducibility differentially regulated in RA synoviocytes and provide potential pathogenic roles of these genes in the hyperplasia of the RA synovium.
Huh
Sung-Jin
SJ
Department of Anatomy and Cell Biology, Institute of Biomedical Science, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul, 133-791, South Korea.
Paik
Doo-Jin
DJ
Chung
Ho-Sam
HS
Youn
Jeehee
J
D048868:Adaptor Proteins, Signal Transducing; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D053455:Caspase 10; D020169:Caspases / Q000235:genetics*; D002478:Cells, Cultured; D051380:GRB2 Adaptor Protein; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D053455:Caspase 10; D020169:Caspases; C105036:interleukin 1beta-converting enzyme 2