Biomedical subjects

O G Ekindjian

Publications and source records attributed to O G Ekindjian.

At least 19 recordsLinked to original sources

PubMed2006

Lack of association between three vascular endothelial growth factor gene polymorphisms and systemic sclerosis: results from a multicenter EUSTAR study of European Caucasian patients.

INTRODUCTION: Systemic sclerosis (SSc) is characterised by disturbed vessel morphology and an overproduction of vascular endothelial growth factor (VEGF). The VEGF gene located on chromosome 6p21.3 has several polymorphisms. OBJECTIVE: To test the hypothesis that disturbed angiogenesis may be related to the genetic background of the VEGF gene. MATERIALS AND METHODS: EUSTAR centres included European Caucasian patients with SSc and matched controls with osteoarthritis. The VEGF gene was genotyped by polymerase chain reaction, followed by restriction enzyme analysis. The 634 C/T and 936 C/G mutations and an 18-base pair insertion/deletion at -2549 of the VEGF promoter region were tested. RESULTS: 416 patients with SSc and 249 controls were included in the study population. Of the patients with SSc, 42% had a diffuse cutaneous subtype, 16% had increased pulmonary arterial pressure and 61% had decreased carbon monoxide diffusion capacity. The genotype frequencies in the patients with SSc and in controls were in Hardy-Weinberg equilibrium. The allele and genotype frequencies of the polymorphisms did not differ between patients with SSc and controls. No association was found between these polymorphisms and disease phenotypes. CONCLUSION: This study shows that there is no association between the three selected functional VEGF polymorphisms and SSc.

Adult↗

PubMed2006

Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy.

OBJECTIVE: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients. METHODS: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers. RESULTS: Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39 nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8 micromol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 micromol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 micromol/L, p=0.02) levels. CONCLUSION: Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.

Adult↗

PubMed2006

Superoxide production and NADPH oxidase expression in human rheumatoid synovial cells: regulation by interleukin-1beta and tumour necrosis factor-alpha.

OBJECTIVES: to evaluate the rheumatoid synovial cell capacity to produce superoxide anion in response to interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha), and to study the NADPH oxidase involvement in this production. MATERIAL AND METHODS: Synovial cells obtained from 7 rheumatoid arthritis (RA), 5 osteoarthritic (OA) patients, and dermal fibroblasts, were stimulated (i) with IL-1beta and TNF-alpha, or (ii) with specific oxidase activators and inhibitors, before studying superoxide production; we also studied NADPH oxidase mRNAs and protein expression, and p47-phox phosphorylation. RESULTS: Constitutive superoxide production by RA cells was increased in comparison to OA cells and dermal fibroblasts, and was stimulated by PMA and ionomycin. This production was increased after cytokine treatment of RA synovial cells. Cytokine-induced superoxide production by RA cells was inhibited by iodonium diphenyl or apocynin, suggesting the involvement of NADPH oxidase. RT-PCR and western blot analysis revealed the presence of p47-phox, gp91-phox and Nox4 in RA and OA cells, and in dermal fibroblasts. P47-phox phosphorylation was enhanced after cytokine-treatment in RA and OA cells, suggesting a PKC-mediated up-regulation of NADPH oxidase. CONCLUSIONS: NADPH oxidase is involved in the superoxide release by RA synovial cells, constitutively and after cytokine up-regulation. These cells express two different homologues (gp91-phox and Nox4).

Aged↗

PubMed2005

Increased plasma soluble CD40 ligand concentrations in systemic sclerosis and association with pulmonary arterial hypertension and digital ulcers.

BACKGROUND: Increased expression of CD40L has been reported on activated CD4+ T lymphocytes in systemic sclerosis. CD40L can be expressed in soluble form (sCD40L). OBJECTIVE: To compare sCD40L concentrations in patients with systemic sclerosis and healthy controls. METHODS: Quantitative sandwich ELISA was used to measure plasma sCD40L in systemic sclerosis (n = 50) and matched healthy controls (n = 20). Patients with systemic sclerosis had limited cutaneous disease (29), digital ulcers (14), pulmonary arterial hypertension (PAH) (10), pulmonary fibrosis on CT (23), positive anti-Scl70 (14), and anti-centromere antibodies (10). Calcium channel blockers were discontinued 72 hours before measurements. RESULTS: Median (range) sCD40L concentration (pg/ml) was higher in systemic sclerosis than in controls (495 (10 to 7720) v 79 (50 to 118); p = 0.003), in limited cutaneous disease v diffuse disease (620 (20 to 7720) v 250 (10 to 2690); p = 0.005), in patients with digital ulcers v those without (1430 (36 to 7720) v 370 (10 to 2320); p = 0.002), and in those with PAH v those without (995 (15 to 3850) v 400 (10 to 7720); p = 0.048). sCD40L correlated with pulmonary arterial pressure estimated by Doppler echocardiography (r = 0.41; p = 0.005). CONCLUSIONS: The soluble form of CD40L is increased in plasma in systemic sclerosis and may be associated with vascular complications of the disease.

Adult↗

PubMed2003

N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers.

OBJECTIVE: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine-type calcium-channel blocker (DTCCB) in patients with systemic sclerosis (SSc). METHODS: We evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean +/- SD age 56 +/- 11 years and mean +/- SD duration of cutaneous disease 9 +/- 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT-proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6-9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline). RESULTS: At baseline, 13 patients had high NT-proBNP values for their ages. High NT-proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT-proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT-proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06). CONCLUSION: NT-proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT-proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.

Aged↗

PubMed2001

Tetracyclines inhibit nitrosothiol production by cytokine-stimulated osteoarthritic synovial cells.

OBJECTIVE AND DESIGN: To evaluate the capacity of doxycycline and minocycline to inhibit NO production and N-nitrosation reactions in vitro. METHODS: Synovial cells obtained from 6 patients with osteoarthritic joint disease were incubated for 24 hours with (i) or without (ii) IL-1beta (1 ng/ml), TNF-alpha (500 pg/ml), IFN-gamma (10(4) U/ml) plus minocycline or doxycycline (10(-4) to 10(-6) M), diclofenac (10(-5) M), or cortisol (10(-5) M). Nitrosothiols were determined by fluorimetry, nitrite by the Griess reaction, nitrate by a spectrophotometric assay using oxidation by nitrate reductase and iNOS by immunoblotting. RESULTS: After 24 hours of stimulation, the level of NO production was much higher than that in untreated cells: about 5.5 times higher for nitrosothiols, 5.2 times higher for nitrate and about 3.5 times higher for nitrite. Doxycycline and minocycline induced a dose-dependent decrease in the production of nitrosothiols, nitrate and nitrite, and inhibited the synthesis of the iNOS protein. Doxycycline and minocycline inhibited the N-nitrosation reaction of DAN effectively, with IC50 values close to 100 microM. Diclofenac and cortisol had no effect. CONCLUSION: This study provides new information on the mechanism by which tetracyclines exert anti-inflammatory effects, via inhibiting nitrosothiols.

Anti-Bacterial Agents↗

PubMed2001

Variability in urinary excretion of bone resorption markers: limitations of a single determination in clinical practice.

In this study we assessed the within and between-subject variability of the concentrations of two urinary markers, free deoxypyridinoline (DPD) and C telopeptide (CTX-I), in healthy patients with the aim of setting reliable thresholds to enable physicians to take decisions about individual patients with confidence.Between-subject variability for the women was 25.4% for DPD and 38.2% for CTX-I, and for the men was 12.9% for DPD and 23.8% for CTX-I. The coefficients of variation were similar for daily, weekly and monthly determinations, giving means of 13.8 and 28.1% for DPD and CTX-I respectively. Critical difference (CD) was lower for DPD than for CTX-I (about 44 and 80% respectively). The number of samples required to determine the true mean with a CD at the 5% level was 29 for DPD and more than 113 for CTX-I.DPD was the least biologically variable. One determination was not sufficient to determine bone resorption status and a 44% decrease in DPD levels and an 80% decrease in CTX-I levels were required to demonstrate the efficacy of antiresorptive therapy in individual patients.

Adult↗

PubMed2001

Low levels of nitric oxide (NO) in systemic sclerosis: inducible NO synthase production is decreased in cultured peripheral blood monocyte/macrophage cells.

OBJECTIVE: To investigate nitric oxide (NO) production and inducible NO synthase expression by cultured peripheral blood mononuclear cells (PBMC) in patients with systemic sclerosis (SSc). METHODS: Eighteen patients with SSc were compared with two control groups: 16 patients with rheumatoid arthritis (RA) and 23 patients with mechanical sciatica. Nitrate was determined by fluorimetry in plasma and by spectrophotometry in supernatants. Inducible NO synthase (iNOS) was detected in cultured PBMC by immunofluorescence, immunoblotting and flow cytometry with or without treatment of the cells with interleukin (IL) 1beta+ tumour necrosis factor alpha (TNF-alpha), IL-4 or interferon gamma (IFN-gamma) from day 1 to day 5. RESULTS: NO metabolite concentrations were lower in SSc patients (mean+/-s.e.m. 34.3+/-2.63 micromol/l) than in RA (48.3+/-2.82 micromol/l; P<0.02) and sciatica (43.3+/-5.24 micromol/l; P<0.03) patients. iNOS was detected in cultured monocytes in all three groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. CONCLUSIONS: The concentrations of NO metabolites are decreased in SSc patients and the metabolism of these compounds in PBMC is altered. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may have therapeutic implications.

Adult↗

PubMed2000

System A neutral amino acid transporter regulation by interleukin-1beta in human osteoarthritic synovial cells: evidence for involvement of prostaglandin E(2) as a second messenger.

We studied the long-terms effects of interleukin-1beta (IL-1beta; 3 to 6 h) on alpha-(methylamino) isobutyric acid (MeAIB), a nonmetabolizable amino acid transported by system A. We found that IL-1beta induced a large decrease in MeAIB uptake by human osteoarthritic synovial cells and a concomitant increase in prostaglandin E(2) (PGE(2)) synthesis. Therefore, we investigated whether PGE(2) acts as a mediator for the long-term action of IL-1beta. We found that exogenous PGE(2) inhibited MeAIB uptake, and that AH6809, a PGE(2) receptor antagonist, inhibited IL-1beta-mediated MeAIB uptake. To identify the enzymes involved in the IL-1beta-mediated synthesis of PGE(2) that inhibits MeAIB uptake, we studied the expression of secreted (s) and cytosolic (c) phospholipase A(2) (PLA(2)). Because both were expressed, we selected a broad spectrum of inhibitors to determine which of the two PLA(2)s was involved. We used AACOCF3, a cPLA(2) inhibitor, and dithiothreitol (DTT) and bromophenacyl bromide (BPB), which are sPLA(2) inhibitors. Our results suggest that the PLA(2) involved in the IL-1beta-mediated synthesis of PGE(2) was sPLA(2). We also showed the expression of cyclooxygenase (COX)-2 and its partial involvement using a potent selective COX-2 inhibitor, L-745337. These findings provide insight into the mechanisms underlying the IL-1beta-mediated regulation of transport system A. The Il-1beta-induced inhibition of MeAIB uptake in human osteoarthritic synovial cells thus seems to be essentially mediated by PGE(2) production via the activation of sPLA(2) and the partial activation of COX-2.

Amino Acid Transport Systems↗

PubMed2000

Nitric oxide modifies glycolytic pathways in cultured human synoviocytes.

Nitric oxide (NO) is a free radical produced during inflammation following activation of an inducible NO synthase by pro-inflammatory cytokines such as IL-1beta. Since both NO and IL-1beta are involved in the physiopathology of inflammatory arthropathies, we investigated the effects of exogenous NO on glycolytic pathways in cultured human osteoarthritic synovial cells. NO generated from S-nitroso-N-acetyl penicillamine (SNAP) or sodium nitroprusside (SNP) inhibited glucose uptake (by 50% after 1 h of incubation) and lactate production by 16% (SNAP) and 8.5% (SNP) after 3 h. Both NO donors also reduced production of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme of the glycolytic pathway. This effect was reversed by haemoglobin, a NO scavenger with higher affinity for the radical. In contrast, the effect on glucose uptake appeared to be irreversible.

Cell Survival↗

PubMed1999

Reactive oxygen species induce apoptosis of synoviocytes in vitro. Alpha-tocopherol provides no protection.

Reactive oxygen species (ROS) are released during the inflammation of the synovial membrane associated with cartilage degradation in osteoarthritis. In this work, we exposed synoviocytes to superoxide anions at concentrations that may cause either apoptosis or necrosis. We studied membrane organization, dehydrogenase mitochondrial activity and nuclear morphology and integrity, to determine the nature of the death process initiated by superoxide anions and tried to counteract ROS effects with alpha-tocopherol. We found that oxidative stress caused synoviocytes to undergo a process of cell death of an apoptotic nature rather than necrotic. Mitochondrial injury occurred at an early stage, and the FITC-annexin-V-positive/propidium iodide-positive cells occurred later than the metabolic changes. DNA strand breaks were evident at 8 h and nuclear condensation at 24 h. No LDH activity was detected in culture supernatants. In our experimental conditions, alpha-tocopherol had little effect on stress damage; the antioxidant properties of this molecule did not affect the apoptosis caused by superoxide anions.

Apoptosis↗

PubMed1999

Is alpha-ketoisocaproyl-glutamine a suitable glutamine precursor to sustain fibroblast growth?

BACKGROUND: Glutamine is considered an essential nutrient for cellular growth. AIM: To test the suitability of alpha-ketoisocaproyl-Gln (Kic-Gln) as a new glutamine (Gln) precursor to sustain human fibroblast growth. METHODS: [3H] thymidine uptake into cellular DNA of human fibroblasts. Extracellular and intracellular amino acid patterns were determined with peptides and acylated compounds. RESULTS: L-alanyl-L-glutamine (used here as a recognized Gln precursor) promoted DNA synthesis, while N-acetyl-L-glutamine (used here as a negative control since it is known to be a poor Gln precursor) and alpha-ketoisocaproyl-glutamine had no effect. Alanyl-glutamine progressively gave rise to free glutamine in the growth medium. In contrast, glutamine supplied in acylated form was poorly available and did not appear in free form in the medium. In addition, only alanyl-glutamine increased intracellular glutamine and glutamate levels. In contrast, Kic-Gln was able to sustain net protein synthesis as judged by total protein content and reduced intracellular levels of most essential amino acids. CONCLUSION: Kic-Gln appears to be a poor extra-cellular precursor of Gln to sustain cell growth.

Biological Availability↗

PubMed1999

Apoptosis induced by nitric oxide is associated with nuclear p53 protein expression in cultured osteoarthritic synoviocytes.

OBJECTIVE: Nitric oxide (NO) is a free radical molecule endogenously produced by NO synthases that may play a critical role in inflammation. It inhibits cell proliferation and may be involved in the induction of apoptosis in various cellular models. Recently, the presence of apoptotic cells was reported in the synovium of osteoarthritic (OA) patients. The aim of this study was to determine whether synovial fibroblasts are target cells for NO-induced apoptosis. The expression of p53 protein was also studied to evaluate the ability of synovial cells to repair DNA fragmentation. METHODS: Synoviocytes from OA patients were treated with two NO donors: sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Apoptosis was analysed by transmission electron microscopy. DNA content was evaluated by flow cytometric analysis after propidium iodide staining and recognition of DNA strand break determined by the TUNEL (TdT-mediated dUTP nick end labeling) method. P53 protein expression was studied by immunofluorescence using a monoclonal antibody. RESULTS: After 6 hours, cells treated with NO donors (1.25 mM) showed a cytoplasmic condensation and vacuolization. DNA strand break analysis by the TUNEL method confirmed the presence of a DNA fragmentation after 24 hours of NO treatment. There was also a progressive decrease in the DNA diploid peak in response to NO donors. In parallel, p53 protein, constitutively expressed in cytoplasmic synovial cells, showed markedly increased expression after a 6-hour NO exposure and displayed prominent nuclear staining after 12 hours. CONCLUSIONS: This study demonstrates the potential role of NO for the induction of synoviocyte apoptosis in OA. The increased expression of p53 in the nucleus may play a protective role in the control of apoptosis.

Aged↗

PubMed1999

Discrimination of osteoarthritic and rheumatoid human synovial cells in culture by nuclear image analysis.

Rheumatoid arthritic (RA) and osteoarthritic (OA) synovial cells in culture differ in their metabolic and proliferative behaviour. To assess links between these properties and nuclear changes, we used image analysis to study chromatin texture, together with nuclear morphometry and densitometry of OA and RA cells in primary culture. Chromatin pattern at the third day (D3) was heterogeneous and granular with chromatin clumps whereas at the final stage (D11) of culture a homogeneous and finely granular chromatin texture was observed. This evolution indicates global chromatin decondensation. These characteristics were more marked for RA than for OA nuclei. At each culture time, RA nuclei could be discriminated with high confidence from OA ones from parameters evaluating the organization of the chromatine texture. Nuclear image analysis is thus a useful tool for investigating synovial cell biology.

Arthritis, Rheumatoid↗

PubMed1999

Nitric oxide synthase is expressed in the lymphomononuclear cells of synovial fluid in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the expression of inducible nitric oxide synthase (iNOS) in subpopulations of peripheral blood and synovial fluid (SF) leukocytes in patients with rheumatoid arthritis (RA). METHODS: iNOS was detected in peripheral blood and SF samples after cell permeabilization, by 2 color immunofluorescence flow cytometry. Samples from 14 patients with RA and 8 with osteoarthritis (OA) were studied. Nitrite concentration was determined by Griess reaction, interleukin 1beta and tumor necrosis factor alpha by an immunoenzymatic assay, and C-reactive protein (CRP) by an immunonephelometric method. RESULTS: In SF, iNOS was detected in 11 of 14 patients with RA and 2 of 8 with OA. In blood cells, iNOS was detected in 8 of 14 patients with RA and none of the OA group. iNOS was consistently detected in monocytes and was not detected in granular cells. In RA, there was no correlation between the number of iNOS positive mononuclear cells and cytokine concentrations. CRP concentration was correlated with the number of iNOS positive mononuclear cells in RA SF samples. CONCLUSION: SF mononuclear cells from patients with RA express iNOS and are involved in NO production in the joint. The number of positive cells is correlated with CRP concentration, suggesting the implication of NO production in the inflammatory process.

Adult↗

PubMed1998

Biochemical markers as predictors of bone mineral density changes after GnRH agonist treatment.

To evaluate bone biochemical markers as predictors of the efficacy of a hormone replacement therapy (HRT), we studied the bone changes induced by the cessation and return of ovarian function in 28 patients treated for 6 months with a GnRH agonist. This model reproduced the effects observed in postmenopausal women with high bone turnover treated with HRT. At the end of the treatment, Z scores were 1.8 +/- 0.3 for Crosslaps (CTx) and deoxypyridinoline (D-Pyr), and 1.1 +/- 0.2 for bone alkaline phosphatase (B-ALP) and osteocalcin (OC). This indicated an imbalance in bone remodeling with a high bone resorption. Bone mineral density (BMD) fell by 4.2 +/- 2.5%. The changes in BMD between the 6th and 12th months were 0. 34 +/- 2.24 and -1.73 +/- 3.25% at the lumbar spine and the femoral neck, respectively. Biochemical markers except urinary calcium and hydroxyproline measured at 6 months were positively correlated with the BMD changes at the lumbar spine. After the resumption of menstruation, 13 of 28 women displayed positive spine BMD changes between the 6th and 12th months; in this group, bone biochemical markers measured at 6 months were significantly higher (P = 0.02). Stepwise regression analysis showed that the association of B-ALP and D-Pyr measured at 6 months explained 40% of BMD variance and the association of B-ALP, PTH, and estradiol 56%. We conclude that measuring individual biochemical bone markers can help to predict the bone effect of an increase in the circulating estradiol in women with ovarian deficiency.

Adult↗

PubMed1997

Nitric oxide as S-nitrosoproteins in rheumatoid arthritis.

OBJECTIVE: Nitric oxide (NO) is a free radical involved in inflammation and immune reactions. The presence of NO is usually assessed by assaying its degradation products, nitrite and nitrate. NO binds to thiol-containing proteins to form S-nitrosoproteins (S-NP). The aim of this study was to investigate the presence of S-NP, together with nitrite and nitrate, in patients with rheumatoid arthritis (RA). METHODS: Forty patients with RA were studied and compared with 24 patients with osteoarthritis (OA) and 21 control subjects. Fourteen patients were treated with 3 consecutive pulses of methylprednisolone for flares of RA. Nitrite was measured by the Griess reaction, and nitrate by a spectrophotometric assay using nitrate reductase. Spectrofluorometry coupled with the inner filter effect was used for the measurement of S-NP. RESULTS: S-NP was detected in all RA samples, both in serum and synovial fluid (SF). Serum and articular S-NP concentrations were correlated (P < 0.03). In RA, nitrite and S-NP levels were higher in SF than in serum; higher SF levels of the 3 compounds were observed in RA than in OA. S-NP levels in RA patients decreased significantly (P < 0.03) after pulse methylprednisolone treatment, in parallel with the clinical improvement. CONCLUSION: S-NP, a biologically active form of NO, was consistently present in RA, with higher concentrations within the arthritic joint. S-NP assays should be added to nitrite and nitrate assays for the evaluation of NO metabolism. S-NP could be a stable storage form of active NO in RA, and its measurement could be useful in evaluating pharmacologic interventions that modulate NO generation.

Arthritis, Rheumatoid↗

PubMed1997

IL-1 modifies system A transport activity in human rheumatoid synovial cells.

Given the importance of interleukin-1 in both rheumatic diseases and the modulation of cell metabolic activities, we studied the action of this cytokine on the neutral amino acid transport A system on rheumatoid synovial cells. In these cells IL-1 (1 ng/ml) induced amino transport stimulation from 5 min to 5 h. This effect was obtained only after a starvation period. No concentration-related effect was found for IL-1-stimulated MeAIB uptake, and the IL-1-mediated MeAIB uptake stimulation is independent of protein synthesis. Neosynthesis or post-translational maturation of protein transport is a prerequisite for obtaining this effect. In conclusion, rheumatoid synovial cells exhibit a higher sensitivity for IL-1 than osteoarthritic ones, probably related to their intense metabolic activity.

Amino Acids↗