Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis
-
Arthritis, Rheumatoid / etiology*
-
Arthritis, Rheumatoid / metabolism
-
Arthritis, Rheumatoid / pathology
-
CASP8 and FADD-Like Apoptosis Regulating Protein / biosynthesis
-
CASP8 and FADD-Like Apoptosis Regulating Protein / physiology*
-
Cell Line
-
Cell Proliferation / drug effects
-
Fibroblasts / cytology
-
Fibroblasts / drug effects
-
Fibroblasts / metabolism
-
Gene Expression Regulation
-
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
-
Humans
-
Mitogen-Activated Protein Kinases / physiology*
-
Neoplasm Proteins / biosynthesis
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / physiology*
-
Nuclear Proteins / biosynthesis
-
Nuclear Proteins / genetics
-
Nuclear Proteins / physiology*
-
RNA-Binding Proteins
-
Synovial Membrane / cytology*
-
Up-Regulation
Substances
-
CASC3 protein, human
-
CASP8 and FADD-Like Apoptosis Regulating Protein
-
Neoplasm Proteins
-
Nuclear Proteins
-
RNA-Binding Proteins
-
Granulocyte-Macrophage Colony-Stimulating Factor
-
Mitogen-Activated Protein Kinases