Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unclear etiology. This study was conducted to identify critical factors involved in the synovial hyperplasia in RA pathology. We applied cDNA microarray analysis to profile the gene expressions of RA fibroblast-like synoviocytes (FLSs) from patients with RA. We found that the MLN51 (metastatic lymph node 51) gene, identified in breast cancer, is remarkably upregulated in the hyperactive RA FLSs. However, growth-retarded RA FLSs passaged in vitro expressed small quantities of MLN51. MLN51 expression was significantly enhanced in the FLSs when the growth-retarded FLSs were treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) or synovial fluid (SF). Anti-GM-CSF neutralizing antibody blocked the MLN51 expression even though the FLSs were cultured in the presence of SF. In contrast, GM-CSF in SFs existed at a significant level in the patients with RA (n = 6), in comparison with the other inflammatory cytokines, IL-1beta and TNF-alpha. Most RA FLSs at passage 10 or more recovered from their growth retardation when cultured in the presence of SF. The SF-mediated growth recovery was markedly impaired by anti-GM-CSF antibody. Growth-retarded RA FLSs recovered their proliferative capacity after treatment with GM-CSF in a dose-dependent manner. However, MLN51 knock-down by siRNA completely blocked the GM-CSF/SF-mediated proliferation of RA FLSs. Taken together, our results imply that MLN51, induced by GM-CSF, is important in the proliferation of RA FLSs in the pathogenesis of RA.
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PMID:MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis. 1710 Oct 62

One of the characteristic features of the pathogenesis of rheumatoid arthritis is synovial hyperplasia. We have reported previously that metastatic lymph node 51 (MLN51) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis. In this study, we have found that: (1) GM-CSF-mediated MLN51 upregulation is attributable to both transcriptional and post-translational control in rheumatoid arthritis fibroblast-like synoviocytes; (2) p38 mitogen-activated protein kinase plays a key role in the upregulation of MLN51; and (3) FLICE-inhibitory protein is upregulated downstream of MLN51 in response to GM-CSF, resulting in the proliferation of fibroblast-like synoviocytes. These results imply that GM-CSF signaling activates mitogen-activated protein kinase, followed by the upregulation of MLN51 and FLICE-inhibitory protein, resulting in fibroblast-like synoviocyte hyperplasia in rheumatoid arthritis.
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PMID:FLIP and MAPK play crucial roles in the MLN51-mediated hyperproliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis. 1851 26

One of the varied characteristic features of the pathogenesis of rheumatoid arthritis (RA) is synovial hyperplasia. Fibroblast-like synoviocytes (FLSs) play a key role in the development of sustained inflammation in arthritic joints. We have reported previously that metastatic lymph node 51 (MLN51) is involved in the proliferation of FLSs in the pathogenesis of RA. Interestingly, the overexpression of MLN51 was observed only in RA FLSs, but not in osteoarthritis FLSs, possibly expecting that MLN51 may be a RA-specific marker. Additionally, we found that granulocyte-macrophage colony-stimulating factor signaling activates mitogen-activated protein kinase, followed by the upregulation of MLN51 and FLICE-inhibitory protein, resulting in FLS hyperplasia in RA. Based on these studies, we could be firm that MLN51 is a key factor in FLS hyperplasia of RA patients.
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PMID:Metastatic lymph node 51 and fibroblast-like synoviocyte hyperproliferation in rheumatoid arthritis pathogenesis. 2132 27