A cross-talk between RNA splicing and signaling pathway alters Fas gene expression at post-transcriptional level: alternative splicing of Fas mRNA in the leukemic U937 cells.

It is now widely accepted that alternative splicing is a mechanism that is responsible for generating protein complexity at low genetic cost. However, little is known about molecular mechanisms that govern alternative splicing of key apoptotic regulators. Here we investigate the effect of pro-apoptotic stimuli on alternative splicing of Fas mRNA by means of reverse transcription-polymerase chain reaction (RT-PCR).

IFN-gamma/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: novel finding of cycloheximide-regulating death receptor expression.

The pathway of interferon gamma (IFN-gamma-induced suppression in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated endothelial cell apoptosis was investigated. rTRAIL triggered apoptosis of human umbilical vein endothelial cells (HUVECs) in a type II cell death manner. IFN-gamma pretreatment significantly suppressed the expression of death receptor 4 (DR4) and DR5 on HUVECs, and inhibited apoptosis in response to TRAIL.

Regulation of alternative splicing of caspase-2 through an intracellular signaling pathway in response to pro-apoptotic stimuli.

Alternative splicing is an important mechanism in the generation of functionally distinct products from the same gene. Some apoptosis-regulating genes also undergo alternative splicing, generating splice variants that antagonzie normal transcripts on apoptosis. For example, caspase-2 is alternatively spliced, leading to exon 9-lacking caspase-2L (proapoptotic) and exon 9-containing caspase-2S (antiapoptotic) transcripts.

Nitric oxide acts on the mitochondria and protects human endothelial cells from apoptosis.

Proliferation of small blood vessels in synovial tissues is one of the pathologic features of rheumatoid arthritis. In this study we tested the hypothesis that nitric oxide (NO) protects endothelial cells (ECs) against apoptogenic agents in vitro. Human umbilical-vein endothelial cells (HUVECs) were cultured with and without NO donor S -nitro- N -acetylpenicillamine (SNAP) and further incubated in the presence or absence of Z-leucine-leucine-leucine-aldehyde (LLL-CHO), etoposide, or C2-ceramide.

Transient appearance of lactate dehydrogenase (LDH)-linked immunoglobulin and thyroid dysfunction at the postpartum period.

Here, we report a 28-year-old woman who transiently showed lactate dehydrogenase (LDH)-linked immunoglobulin during postpartum thyroiditis. She demonstrated high levels of serum LDH (794 IU/l) and thyroid hormones 7 months after delivery. Electrophoretic isoenzyme analysis of LDH showed an abnormal broadband caused by LDH-linked immunoglobulin (IgG-kappa).

A novel mutation (T61I) in the gene encoding tumour necrosis factor receptor superfamily 1A (TNFRSF1A) in a Japanese patient with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) associated with systemic lupus erythematosus.

Objective: To identify potential mutations in the tumour necrosis factor receptor superfamily 1A gene (TNFRSF1A) in a Japanese female patient with recurrent fever complicated by systemic lupus erythematosus (SLE), and in her family members.

Methods: DNA sequencing of exons 1-10 of the TNFRSF1A gene was performed to determine mutations that might be associated with the tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Moreover, the TNFRSF1A gene was examined in Japanese patients with autoimmune diseases, including SLE, rheumatoid arthritis (RA), mixed connective tissue disease (MCTD) and Behçet's disease, and in healthy Japanese controls.

Osteoprotegerin (OPG) acts as an endogenous decoy receptor in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells.

We examined the role of osteoprotegerin (OPG) on tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in rheumatoid fibroblast-like synovial cells (FLS). OPG protein concentrations in synovial fluid from patients with rheumatoid arthritis (RA) correlated with those of interleukin (IL)-1beta or IL-6. A similar correlation was present between IL-1beta and IL-6 concentrations.

Cytokines regulate fibroblast-like synovial cell differentiation to adipocyte-like cells.

Objectives: Our recent work showed that fibroblast-like synovial cells (FLS) could differentiate into adipocyte-like cells in vitro in response to stimulation with peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand. The aim of the present study was to determine the role of cytokines in the regulation of FLS differentiation to adipocyte-like cells.

Methods: FLS isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from normal synovial tissues were incubated with the synthetic PPAR gamma ligand troglitazone to induce adipocyte-like differentiation of the cells.

Anti-apoptogenic function of TGFbeta1 for human synovial cells: TGFbeta1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli.

Objective: To investigate anti-apoptogenic mechanism of transforming growth factor beta1 (TGFbeta1) towards synovial cells.

Methods: Isolated synovial cells, treated or not with TGFbeta1, were cultured in the presence or absence of anti-Fas IgM, proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or C2-ceramide. After cultivation, apoptosis of synovial cells was examined by the presence of hypodiploid DNA(+) cells, the presence of terminal deoxy (d)-UTP nick end labelling(+) cells (TUNEL(+) cells), activation of caspases, and disruption of mitochondrial transmembrane potential (DeltaPsim).

Protection of mitochondrial perturbation by human T-lymphotropic virus type 1 tax through induction of Bcl-xL expression.

This study was designed to determine the inhibitory role of human T-lymphotropic virus type 1 (HTLV-1) tax against apoptotic cell death. We used JPX-9 cells, a Jurkat subclone generated by the stable introduction of a tax expression-plasmid vector, and induced tax expression in JPX-9 cells with CdCl2. Expression of Bcl-2, Bcl-xL, and Bax in JPX-9 cells was assessed with Western blot analysis.

Characterization of anticytoplasmic antibodies in patients with systemic autoimmune diseases.

Abstract We characterized the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) using human epithelial (HEp-2) cells as substrates, and identified autoantigens using enzyme-linked immunosorbent assay (ELISA) and cognate RNA immunoprecipitation techniques in cytoplasmic antibody-positive sera (CA(+)) in patients with systemic autoimmune diseases. Twenty-three sera (3.7%) of 630 patients were found to have a cytoplasmic staining pattern by IF on HEp-2 cells.

Akt is an endogenous inhibitor toward tumor necrosis factor-related apoptosis inducing ligand-mediated apoptosis in rheumatoid synovial cells.

Akt is known to be activated in the rheumatoid synovial tissues. We examined here functional role of Akt during tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis in rheumatoid synovial cells. Rheumatoid synovial cells in vitro were rapidly committed to apoptosis in response to TRAIL in mitochondria-dependent manner whereas Akt and extracellular signal-regulated kinase (ERK) were also phosphorylated.

Granzyme B leakage-induced cell death: a new type of activation-induced natural killer cell death.

Activation-induced natural killer (NK) cell death is very rapid compared to activation-induced T or B cell death. Here we show that NK cell activation is accompanied by the leakage of granzymeB from intracellular granules into the cytoplasm. Evidence for granzyme B leakage includes the formation of granzyme B/serine proteinase inhibitor 9 (PI-9) complexes that are detected by immunoprecipitation as well as colocalization of granzyme B and PI-9 detected by immunocytochemistry.

A case of amyloidosis secondary to rheumatoid arthritis complicated with Graves' ophthalmopathy.

Abstract We report the case of a 73-year-old woman who suffered from amyloidosis secondary to rheumatoid arthritis (RA) complicated with Graves' ophthalmopathy. She had goiter, diplopia, and exophthalmos with polyarthralgia. We diagnosed Graves' ophthalmopathy with thyroid-stimulating hormone (TSH)-receptor antibodies (TBII and TSAb).

Clinical outcome and survival of secondary (AA) amyloidosis.

Objective: In order to predict the clinical outcome of secondary (AA) amyloidosis patients with rheumatic diseases, we studied the clinical features at presentation of AA amyloidosis.

Methods: We investigated the clinical characteristics and survival of 42 patients with biopsy-proven AA amyloidosis who were followed up in our department from 1983 to 2001.

Results: A presenting factor which adversely influenced clinical outcome was a raised serum creatinine concentration at the time AA amyloidosis was diagnosed.

Modulation of the expression of membrane-bound CD54 (mCD54) and soluble form of CD54 (sCD54) in endothelial cells by glucosyl transferase inhibitor: possible role of ceramide for the shedding of mCD54.

1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) is a synthetic inhibitor toward glucosyl transferase. Here, we showed the functional role of sphingolipids on CD54 expression of endothelial cells (ECs) by the use of PDMP. CD54 mRNA expression in human umbilical vein endothelial cells (HUVECs) was not changed by PDMP; however, PDMP treatment significantly enhanced the expression of membrane-bound CD54 (mCD54) on HUVECs.

Atypical mycobacteriosis in two patients with rheumatoid arthritis.

Abstract We report two cases of rheumatoid arthritis (RA) with atypical mycobacteriosis. Opportunistic infections are critical complications for rheumatic diseases. The use of steroids or immunosuppressants may increase the risk of opportunistic infections.

Expression of membrane-type 1 matrix metalloproteinase in rheumatoid synovial cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is thought to be a putative regulator of pro-gelatinase A (MMP-2) in the rheumatoid synovium. In this study, we examined the effects of IL-1beta, one of the inflammatory cytokines, on the expression of MT1-MMP and the activation of pro-MMP-2 using rheumatoid synovial cells. We also studied the effects of KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid), a new disease-modifying anti-rheumatic drug (DMARD), on MT1-MMP expression of rheumatoid synovial cells.

New disease-modifying antirheumatic drug 2 acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298) selectively augments activation-induced T cell death.

We examined in this study whether the newly developed disease-modifying antirheumatic drug (DMARD) 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298) augments activation-induced T cell death. Peripheral blood (PB) T cells, isolated from healthy donors, were activated by incubation with interleukin-2 (IL-2) followed by further culture with 12-0-tetradecanoyl phorbol 13-acetate (PMA) and ionomycin in the presence or absence of KE-298. The apoptosis of activated T cells was examined by flow cytometric determination of hypodiploid DNA.

A novel role for interleukin-18 in human natural killer cell death: high serum levels and low natural killer cell numbers in patients with systemic autoimmune diseases.

Objective: Patients with systemic autoimmune diseases have been reported to have reduced numbers of peripheral blood natural killer (NK) cells compared with healthy subjects. The ability of selected cytokines to trigger NK cell death prompted us to compare the levels of peripheral blood cytokines with the numbers of NK cells in patients with various systemic autoimmune diseases.

Methods: We used enzyme-linked immunosorbent assays to measure the concentration of selected cytokines (interleukin-18 [IL-18], IL-15, IL-12, IL-2, interferon-gamma [IFNgamma], and tumor necrosis factor alpha [TNFalpha]) in sera from 58 patients with systemic autoimmune diseases and 33 healthy controls.

Regulation of cyclooxygenase-2 expression in human osteoblastic cells by N-acetylcysteine.

Cyclooxygenase (COX) plays a pivotal role in the inflammatory process of inflammatory arthropathies. Inflammatory cytokines induce COX-2 expression in osteoblasts of inflamed joints, followed by osteoclast activation. The inhibition of COX-2 expression could help prevent prostaglandin E2 secretion, followed by osteoclast activation for bone destruction and resorption.

IL-1-mediated expression of membrane type matrix-metalloproteinase in rheumatoid osteoblasts.

Objective: To determine whether the activation of metalloproteinases can be achieved by the interaction of the inflammatory cytokine, IL-1 beta, with rheumatoid osteoblasts.

Results: MMP-2 is not secreted by rheumatoid osteoblasts as a proenzyme; however, IL-1 beta stimulation induced the secretion of MMP-2 as an active form from rheumatoid osteoblasts. This MMP-2 activating activity was detected significantly in IL-1 beta-stimulated rheumatoid osteoblasts.