Angiopoietin 1 directly induces destruction of the rheumatoid joint by cooperative, but independent, signaling via ERK/MAPK and phosphatidylinositol 3-kinase/Akt.

Objective: To determine whether angiopoietin 1 (Ang-1) potentiates overgrowth of the synovium and joint degradation in rheumatoid arthritis (RA), and to clarify the cell-signaling mechanisms of Ang-1 in the rheumatoid joint.

Methods: Expression of Ang-1, TIE-2 (a receptor for Ang-1), and matrix metalloproteinase 3 (MMP-3) was studied by immunohistochemistry. Activation of the ERK/MAPK and phosphatidylinositol (PI) 3-kinase/Akt pathways and of NF-kappaB was determined by Western blotting and an NF-kappaB p65 DNA binding activity assay, respectively.

Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells.

Objective: To examine the promoter activity and protein expression of the death receptor 3 gene DR3, a member of the apoptosis-inducing Fas gene family, with particular reference to the methylation status of its promoter region in rheumatoid arthritis (RA).

Methods: Genomic DNA was prepared from peripheral blood mononuclear cells obtained from healthy individuals and from patients with RA and synovial cells obtained from patients with RA and osteoarthritis. The methylation status of the DR3 promoter was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction techniques.

Heat shock protein 90 is required for increased DNA binding activity of activator protein-1, a heterodimer of Fos/JunD, in rheumatoid synovial cells under inflammatory stimuli.

We have studied the DNA binding profiles of activator protein-1 (AP-1) involved in synovial overgrowth and osteoporosis in rheumatoid arthritis (RA) in relation to the molecular chaperon heat shock protein 90 (HSP90). The AP-1 binding activity of the nuclear extracts of rheumatoid synovial cells was basically increased as compared with osteoarthritic synovial cells. Upon stimulation with inflammatory cytokines IL-1beta or TNFalpha, the AP-1 binding activity was further increased in rheumatoid synovial cells, and increased AP-1 protein was composed as heterodimers of Fos and JunD which was not known before as a major component of AP-1 in rheumatoid synovial cells.

A case of central nervous system lupus in succession to lupus peritonitis: a difficulty in the differential diagnosis between lupus psychosis and steroid-induced psychosis.

Abstract A 55-year-old woman with well-controlled systemic lupus erythematosus (SLE) suffered from the abrupt onset of massive intractable ascites, which did not respond to conventional diuretic therapy. While treatment with methylprednisolone pulse therapy ameliorated this lupus peritonitis, neuropsychiatric symptoms then appeared. After a diagnosis of the central nervous system (CNS) lupus, pulse therapy was continued and the patient recovered from the lupus psychosis.

Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene duplication is more prevalent in rheumatoid arthritis.

The death receptor 3 (DR3) gene is a member of the apoptosis-inducing Fas gene family. In the current study, fluorescence in situ hybridization (FISH) and Fiber-FISH revealed the existence of a second DR3 gene approximately 200 kb upstream of the original DR3 gene. The existence of the duplicated DR3 gene was confirmed by sequencing the corresponding human artificial chromosome clones as well as with quantitative PCR that measured the ratio of the DR3 gene mutation (Rm), intrinsic to rheumatoid arthritis (RA) patients, by simultaneous amplification of the normal and mutated DR3 sequences.

Human wee1 kinase is directly transactivated by and increased in association with c-Fos/AP-1: rheumatoid synovial cells overexpressing these genes go into aberrant mitosis.

Wee1 kinase downregulates the M-phase promoting factor, a complex of cdc2 and cyclin B kinase, that controls mitotic cell division. We isolated human wee1 kinase gene promoter and found that it contained one AP-1-binding motif in its promoter region (5'-CGAGTCA-3'; -823/-817), through which wee1 kinase gene was directly transactivated by c-Fos/AP-1. In rheumatoid synovial cells, wee1 kinase was increased in conjunction with the increase of c-Fos/AP-1 and the substrate of wee1, cdc2, was phosphorylated.

Alternative splicing variants of the human DBL (MCF-2) proto-oncogene.

The DBL (MCF-2) proto-oncogene is a prototype guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases. In this communication we describe the isolation of three novel splicing variants of Dbl. The prototype Dbl gene (designated var.