title: Regulation of rheumatoid synovial cell growth by ceramide.
abstract: Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.
authors.affiliation: First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Migita
authors.forename: S
authors.initials: S
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Hirai
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: M
authors.initials: M
authors.lastname: Kita
authors.forename: H
authors.initials: H
authors.lastname: Ida
authors.forename: T
authors.initials: T
authors.lastname: Tsukada
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology*
chemical_list: C064769:N-acetylsphingosine; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D013110:Sphingosine