Epstein-Barr virus infection and variants of Epstein-Barr nuclear antigen-1 in synovial tissues of rheumatoid arthritis.

Objective: The objective of the present study was to investigate Epstein-Barr virus (EBV) infection as an environmental factor for the development of rheumatoid arthritis (RA).

Methods: Synovial tissues were collected during surgery from 128 RA and 98 osteoarthritis (OA) patients. DNA was extracted from synovial tissues.

Resistin upregulates chemokine production by fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Background: Adipokines are bioactive hormones secreted by adipose tissues. Resistin, an adipokine, plays important roles in the regulation of insulin resistance and inflammation. Resistin levels are known to be increased in the serum and synovial fluid of rheumatoid arthritis (RA) patients.

Glucocorticoid therapy causes contradictory changes of serum Wnt signaling-related molecules in systemic autoimmune diseases.

The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4 weeks after its initiation.

Apparent Hypothalamic-Pituitary-Adrenal Axis Suppression via Reduction of Interleukin-6 by Glucocorticoid Therapy in Systemic Autoimmune Diseases.

Context: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a serious complication of systemic glucocorticoid therapy.

Objective: To clarify the influence of proinflammatory cytokines on the HPA axis after onset of glucocorticoid therapy in patients with systemic autoimmune diseases.

Patients And Methods: Forty-eight glucocorticoid-naïve patients with systemic autoimmune diseases (28 women) who were starting prednisolone therapy according to our standard regimens were prospectively observed.

Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases.

The growth factor midkine may play a pathophysiological role in rheumatoid arthritis.

Objectives: Midkine (MK) is involved in cell proliferation, differentiation, migration, and survival. In this study, we measured serum MK levels in rheumatoid arthritis (RA) and investigated the correlation of serum MK with RA disease activity. Expression and effect of MK in RA synovial tissue were also examined.

Leptin stimulates interleukin-6 production via janus kinase 2/signal transducer and activator of transcription 3 in rheumatoid synovial fibroblasts.

Objectives: The aim of this study was to determine the influence of leptin on the production of proinflammatory cytokines by rheumatoid synovial fibroblasts (RSFs).

Methods: Synovial tissue was obtained from patients with rheumatoid arthritis (RA). Leptin receptor mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR).

Tacrolimus down-regulates chemokine expressions on rheumatoid synovial fibroblasts: screening by a DNA microarray.

Objective: Although the effects of tacrolimus on T cells are well-known, direct effects on rheumatoid synovial fibroblasts (RSF) remain unclear. We studied the effects of tacrolimus on RSF by a DNA microarray analysis.

Materials And Methods: Tacrolimus and interleukin (IL)-1β were added to cultured RSF.

Changes of serum soluble receptor activator for nuclear factor-κB ligand after glucocorticoid therapy reflect regulation of its expression by osteoblasts.

Context: Osteoporosis is a serious complication of systemic glucocorticoid therapy. The role of serum soluble receptor activator for nuclear factor-κB ligand (RANKL) in glucocorticoid-induced osteoporosis remains unclear.

Objective: The objective of the study was to clarify the influence of serum soluble RANKL on the osteoprotegerin (OPG)/RANKL/receptor activator for nuclear factor-κB system in patients with systemic autoimmune diseases receiving glucocorticoid therapy.

Resistin is associated with the inflammation process in patients with systemic autoimmune diseases undergoing glucocorticoid therapy: comparison with leptin and adiponectin.

Objectives: We investigated the role of adipokines in patients with systemic autoimmune diseases who received glucocorticoid therapy.

Methods: Fifty-two patients with systemic autoimmune diseases who had started glucocorticoid therapy were prospectively enrolled. One hundred forty healthy persons were also studied as controls.

Serum adipokine profiles in Kawasaki disease.

Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease.

Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis.

Objective: Body fat is an important source of hormones and cytokines (adipokines) that not only regulate the energy balance, but also regulate the inflammatory and immune responses. This study investigated the association of clinical conditions with serum levels of adipokines in patients with rheumatoid arthritis.

Methods: Serum levels of resistin, leptin, and adiponectin were measured by enzyme-linked immunosorbent assay in 141 patients (110 women) who fulfilled the 1987 revised criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis and in 146 normal controls (124 women).

Adiponectin stimulates prostaglandin E(2) production in rheumatoid arthritis synovial fibroblasts.

Objective: Adipokines may influence inflammatory and/or immune responses. This study was undertaken to examine whether adiponectin affects the production of prostaglandin E(2) (PGE(2)) by rheumatoid arthritis synovial fibroblasts (RASFs).

Methods: Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery.

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts.

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect.

Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the articular synovial tissues. Although the etiology of RA has not yet been elucidated, physical and biochemical inhibition of synovial hyperplasia, which is the origin of articular destruction, may be an effective treatment for RA. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of RA.

A celecoxib derivative potently inhibits proliferation of colon adenocarcinoma cells by induction of apoptosis.

Background: Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, has a pro-apoptotic effect on colon adenocarcinoma cells via COX-independent mechanisms.

Materials And Methods: The pro-apoptotic effect of N-(2-Aminoethyl)-4-[5- (4-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (TT101), a new derivative of celecoxib, was investigated on the HT-29 and SW480 colon adenocarcinoma cells. Cell proliferation and viability were assessed by incorporation of 5-bromo-2'-deoxyuridine and by the 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, respectively.

A novel celecoxib derivative potently induces apoptosis of human synovial fibroblasts.

We have already demonstrated that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, has a proapoptotic effect on synovial fibroblasts obtained from patients with rheumatoid arthritis (RA). Here we report on the development of two novel derivatives of celecoxib, N-(2-aminoethyl)-4-[5-(4-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (TT101) and 4-[5-(4-aminophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (TT201), including whether these compounds have a proapoptotic effect on synovial fibroblasts. Synovial fibroblasts were harvested from the synovial tissues of patients with RA or osteoarthritis (OA).

[Preventing effects of COX-2 inhibitors on rheumatoid joint destruction].

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX) -2 inhibitors with the potential to reduce the risk of gastrointestinal bleeding, have their crucial role in the control of inflammation. However, they have recently been shown to have a preventing effect against joint destruction by basic studies related to pathophysiology in rheumatoid arthritis. Here we summarize the current knowledge on anti-proliferative action due to apoptosis, suppression of angiogenesis, and suppression of osteoclastic bone resorption by NSAIDs.

Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts.

Background: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide (a constituent of TWHF) could influence the proliferation of rheumatoid synovial fibroblasts (RSF) by induction of apoptosis.

Results: RSF were obtained from RA patients during surgery and were treated with triptolide under various conditions.

Aspirin and sodium salicylate inhibit proliferation and induce apoptosis in rheumatoid synovial cells.

Aspirin has been reported to induce apoptosis in a variety of cell lines. In this study, we examined whether aspirin and sodium salicylate inhibit cell growth and induce apoptosis in rheumatoid synovial cells. Synovial cells were obtained from patients with rheumatoid arthritis, and the cells were treated with aspirin or sodium salicylate (0.

Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors.

Objective: Selective cyclooxygenase 2 (COX-2) inhibitors are now being used as antiinflammatory agents that cause fewer gastrointestinal complications, compared with other antiinflammatory drugs, in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether selective COX-2 inhibitors could induce apoptosis of RA synovial fibroblasts (RASFs).

Methods: RASFs were exposed to selective COX-2 inhibitors, i.

Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells.

Although the influence of selective cyclooxygenase (COX)-2 inhibitors on the proliferation of colon adenocarcinoma cells have been the subject of much investigation, relatively little research has compared the effects of different COX-2 inhibitors. Celecoxib strongly suppressed the proliferation of COX-2 expressing HT-29 cells at 10-40 microM. NS-398 and nimesulide also inhibited cell proliferation, whereas rofecoxib, meloxicam, and etodolac did not.

Nonsteroidal anti-inflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor gamma in rheumatoid synovial cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce apoptosis in a variety of cell lines. In this study, we examined the effect of NSAIDs on the growth and apoptosis of synovial cells from patients with rheumatoid arthritis and analyzed the activation of peroxisome proliferator-activated receptor gamma (PPARgamma) as a possible mechanism of action of NSAIDs. Cell proliferation and viability were assessed from 5-bromo-2'-deoxyuridine incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay, respectively.