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ID PMID Title PublicationDate abstract
10836521 Basic FGF-induced activation of telomerase in rheumatoid synoviocytes. 2000 To investigate the mechanism of persistent proliferation of rheumatoid arthritis (RA) synoviocytes in situ, we examined the activity of telomerase enzyme and the expression of telomerase related factors in cultured synoviocytes. Cultured synoviocytes obtained from patients with rheumatoid arthritis (n = 29), osteoarthritis (OA, n = 18), and traumatic joint disease (TJD, n = 4) were examined. Telomerase activity was detected by TRAP (telomeric repeat amplification protocol) assay, and 12 out of 29 samples of synoviocytes (41%) from RA patients showed a positive telomerase activity, whereas none of the samples from OA and TJD patients showed this activity. Results were confirmed by PCR-ELISA. The telomerase activity was enhanced by basic fibroblast growth factor (bFGF). The mRNA expression of telomerase related factors, such as hTERC, TRF2, and TEP-1, showed no difference between RA and OA synoviocytes. Our results suggest that telomerase is activated in rheumatoid synoviocytes, and that bFGF upregulates the activity of this enzyme in RA synoviocytes.
9678688 Cryptococcal pleural effusion in a patient with chronic renal failure receiving long-term 1998 Jun A 52-year-old woman with a seven-year history of rheumatoid arthritis (RA) was transferred to our department with chronic renal failure to undergo hemodialysis. She had been treated with prednisolone for a long time, and had renal amyloidosis secondary to RA. During her hospitalization, a left pleural effusion developed. Pleural fluid cultured positive for Cryptococcus neoformans (CN), and the CN antigen was detected in both pleural fluid and serum. Chest computerized tomography revealed an infiltrate shadow in the left lower lung field suggestive of CN infection. This was successfully treated with anti-fungal agents. Pleural effusion is an unusual manifestation of pulmonary cryptococcosis. We should consider a diagnosis of CN infection when pleural effusion is observed in compromised patients such as those receiving a long-term corticosteroid treatment.
10725065 Microemulsion formulation of cyclosporin (Sandimmun Neoral) vs Sandimmun: comparative safe 2000 Feb OBJECTIVE: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. METHODS: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. RESULTS: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. CONCLUSION: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.
10366101 Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 ge 1999 Jun OBJECTIVE: To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA). METHODS: The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed. Allelic frequencies and carriage rates were compared between RA patients and controls, between patients with erosive and nonerosive RA, and between patients with or without sustained remission. RESULTS: The RP1 allele of the IL-4 gene was found with a significantly higher frequency in RA patients compared with controls. The combination of an RA-related HLA-DR allele expressing shared epitope and the presence of allele E2 in IL-1beta exon 5 was found to expose patients to an increased risk of erosive disease, with an odds ratio of 8.20 (95% confidence interval 2.59-25.84, P < 0.0001). No significant association was observed between polymorphisms and the occurrence of sustained remission. CONCLUSION: This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.
9259418 Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. 1997 Aug OBJECTIVE: To show the eventual presence and extent of production of matrix metalloproteinase 13 (MMP-13, or collagenase 3) in rheumatoid synovial tissue samples and extracts, and to assess the inhibition characteristics of recombinant MMP-13. METHODS: Immunohistochemical avidin-biotin-peroxidase complex staining/morphometry was used to analyze MMP-13-positive cells in situ. Neutral salt extraction of synovial tissue, electrophoresis of the extract in different buffer systems, and Western blotting were also used. The inhibitory properties of doxycycline, clodronate, pamidronate, and D-penicillamine for recombinant enzyme were determined with a soluble type II collagen assay. RESULTS: MMP-13 was detected in fibroblast- and macrophage-like mononuclear cells in the synovial lining and stroma and in vascular endothelial cells. The overall expression of MMP-13 in these cells in the synovial stroma was high in rheumatoid arthritis (86 +/- 12%) compared with osteoarthritis (17 +/- 5%) patient samples (P = 0.0027). In a high-pH native electrophoresis gel, immunoreactivity to anti-MMP-1 and anti-MMP-13 were clearly separated, with anti-MMP-13-immunoreactive material migrating faster than anti-MMP-1-immunoreactive material. Finally, in contrast to MMP-1 and MMP-8, MMP-13 was found to be relatively resistant to the inhibitory effects of doxycycline and clodronate in vitro. CONCLUSION: Due to its localization in synovial tissue, its substrate profile, increased expression, and relative resistance to known MMP inhibitors, MMP-13 is suggested to play a major role in the pathogenesis of tissue destruction in rheumatoid arthritis.
10923521 [Time selection for RA synovectomy]. 1998 Mar OBJECTIVE: To discuss the time selection for RA synovectomy. METHOD: Eighty-six knees in 64 RA patients underwent synovectomy in 7 years. 8 of the 64 patients were in RA stage I, 26 in II, 24 in III, 8 in IV. The mean age was 43.9 years and the average follow-up period lasted 38.2 months. RESULTS: Pain relief and swelling reduction were significant clinical features after synovectomy. The overall assessment of the effect of synovectomy showed satisfactory results (72.9%) including all RA-I, and RA-II (87.2%). CONCLUSION: If the patients have sustained or intractable joint swollening with exuberant synovium after strict drug therapy over half a year, synovectomy is an appropriate consideration, it is very important to select the time for synovectomy.
10363610 Surgical management of cardiovascular lesions caused by systemic inflammatory diseases. 1999 Apr BACKGROUND: The surgical treatment of cardiovascular disorders caused by inflammatory diseases presents many difficulties, including suture detachment and progression of vascular lesions. We here report the various surgical procedures used to treat these disorders and their long-term outcomes. METHODS: We operated on 14 patients: eight with Takayasu's disease, three with systemic lupus erythematosus, two with rheumatoid arthritis, and one with Behçet's disease. Patients were divided into three groups as follows; patients (n=7) requiring aortic valve replacement; patients (n = 4) requiring reconstruction of the coronary artery; and patients (n = 3) requiring aortic aneurysm repair. RESULTS: There were no early or late deaths in the postoperative follow-up period of 70 +/- 40 months, but there was one operative death. Three patients received postoperative steroids due to progression of the inflammation. However, there were no major complications such as valve detachment, pseudoaneurysmal formation, or occlusion of the bypass conduit. CONCLUSIONS: We conclude that it is crucial to reduce inflammation pre- and postoperatively, to reinforce the suture line, and to carefully select the operative procedures when treating cardiovascular disorders caused by inflammatory diseases.
10881738 Mig, GRO alpha and RANTES messenger RNA expression in lining layer, infiltrates and differ 2000 May To investigate lymphocyte and monocyte recruitment-specific chemokine expression in synovial tissues from patients with rheumatoid arthritis (RA), psoriatic arthritis (PA) and osteoarthritis (OA), synovial membranes and cytocentrifuge preparations of 7 RA, 8 PA and 10 OA patients were examined by in situ hybridisation with antisense probes of Mig, GRO alpha and RANTES and by immunohistochemistry. Patients' local disease activity (swelling and tenderness) in order to was graded and histological evaluation was performed compare these data with their chemokine expression profiles. Mig and RANTES hybridisation signals were detected in the synovial lining layer and in cellular infiltrates, whereas GRO alpha expression was localised exclusively in the lining layer of PA and RA. Cytological analysis revealed Mig and GRO alpha mRNA mainly in monocytic cells expressing KIM6, while RANTES mRNA was demonstrated predominantly in lymphocytic cells expressing CD3. In OA synovial membranes, significantly fewer hybridisation signals were present than in RA and PA synovial membranes. Patients with PA and RA had mild to severe local disease activity, whereas OA patients showed only mild disease activity. Histologically, PA and RA inflammatory scores ranged from 1 to 5, while OA synovium was consistently graded 1. Therefore, we conclude that the differential expression of Mig, GRO alpha and RANTES in resident and in inflammatory cells has an important role in regulating leucocyte traffic in inflammatory arthropathies. The diverse leucocyte specificity of Mig, GRO alpha and RANTES may thus regulate the recruitment of different leucocyte populations, as detected in PA and RA. Therefore, the pattern of cellular infiltration in human synovitis and the corresponding clinical signs of inflammation basically reflect the localisation and expression intensity of chemokines, which may be an important target for future disease modulation.
10093108 Pulmonary manifestations of rheumatic diseases. 1999 The pulmonary manifestations of rheumatic diseases can vary substantially, both in severity and mechanism of injury. There is still relatively little experience with these conditions in the pediatric age group. Perhaps tissue diagnosis will help elucidate the pathophysiology involved and allow for the development of more specific treatment protocols.
9522599 [Heart and autonomic nervous system in connective tissue disorders]. 1997 Dec Heart rate variability (HRV) is a suitable diagnostic tool in identifying patients with autonomic nervous system (ANS) disorders even in pre-clinical stage. We have enrolled in this study all patients with large variety of connective tissue disorders, given the possibility of an involvement of ANS in these diseases. The study population consisted in eighty-five patients (68 females and 17 males), 35 of whom affected by systemic lupus erythematosus, 16 by rheumatoid arthritis, 14 by Sjögren syndrome, 12 by progressive systemic sclerosis, 3 by Behçet syndrome and 5 by antiphospholipid antibodies syndrome. The mean age ranged between 33.7 of patients with lupus erythematosus and 51.8 of those with Sjögren syndrome. As control, we enrolled healthy subjects of different age, divided into two groups, to rule out the aging as potential source of considered parameters alteration. The autonomic function has been evaluated by 24 hours ambulatory monitoring, using a Zymed 1210 Scanner with Zymed 3.74-PC 1990 software. We have considered: in the time domain, the standard deviation of the RR intervals average (SDNN) and the percentage of RR adjacent intervals differing each other more than 50 msec (pNN50); in the frequency domain, the low (LF) and high (HF) frequencies, the LF/HF ratio, and the total power (RT). The HRV parameters resulted abnormal in every type of the connective tissue diseases considered: particularly SDNN, pNN50, LF, HF and RT (p < or = 0.01). IN CONCLUSION: the results of our study suggest that autonomic neuropathy may be present in any kind of connective tissue disorders even in preclinical stage.
10577978 PEGylated recombinant human soluble tumour necrosis factor receptor type I (r-Hu-sTNF-RI): 1999 Nov The proinflammatory cytokine, tumour necrosis factor alpha (TNFalpha) has been shown to play a pivotal part in mediating acute and chronic inflammation. The activities of TNFalpha are modulated by the proteolytic shedding of the soluble extracellular domains of the two TNF receptors, p55 sTNF-RI and p75 sTNF-RII. Amgen Inc has cloned and expressed a recombinant form of a natural inhibitor of TNFalpha, referred to as recombinant human soluble TNF receptor type I (r-Hu-sTNF-RI, sTNF-RI). sTNF-RI is an E coli recombinant, monomeric form of the soluble TNF-type I receptor. A high molecular weight polyethylene glycol (PEG) molecule is attached at the N-terminus position to form the molecule intended for clinical evaluations (PEG sTNF-RI). Preclinical studies to date demonstrate that PEG sTNF-RI is efficacious in rodent models of chronic inflammatory disease including rheumatoid arthritis and Crohn's disease at doses as low as 0.3 mg/kg given every other day. This dose results in plasma concentrations of 0.3 to 0.5 microg/ml. Higher doses with correspondingly higher plasma concentrations yield higher efficacy. It has also demonstrated efficacy in E coli lipopolysaccharide, and Staphylococcus enterotoxin B mediated models of acute inflammation in rodents and primates. Pharmacokinetic studies in mice, rats, cynomolgus monkeys, baboons, and chimpanzees have been conducted with PEG sTNF-RI. Absorption from a subcutaneous dose was slow, with the time to reach maximal plasma concentrations of 24-48 hours in rats, and in monkeys, and 3-29 hours in chimpanzees. The initial volume of distribution of PEG sTNF-RI was essentially equivalent to that of plasma (40 ml/kg). This suggests the protein does not appear to extensively distribute from the systemic circulation with a volume of distribution at steady state (Vss) less than 200 ml/kg in all species studied. These results are consistent with previous experience with PEGylated proteins in which PEGylation decreases both the rate of absorption and the plasma clearance of human recombinant proteins in animals and humans. The use of a PEG molecule will probably provide a more advantageous dosing schedule (that is, less frequent dosing) for the patient compared with a non-PEG sTNF-RI.
9849315 Increased expression of human type IIa secretory phospholipase A2 antigen in arthritic syn 1998 Sep OBJECTIVE: To determine the localisation and level of expression of human type IIa secretory phospholipase A2 (sPLA2) in the synovium of rheumatoid arthritis (RA), osteoarthritis (OA), and non-arthritic (NA) patients and to examine the relation between sPLA2 and histological features of inflammation. METHODS: Immunoperoxidase staining using the anti-sPLA2 monoclonal antibody 9C1 was performed on frozen sections of knee synovium of 10 RA, 10 OA, and 10 NA patients. sPLA2 positive cells were scored on a scale of 0-3 in 10 fields of a representative tissue section from each case. Double labelling immunofluorescence confocal microscopy with antibodies to CD14 or CD45 and 9C1 was used to determine cell type specificity. Inflammation was assessed by semiquantitative scoring of lining layer thickness and mononuclear cell infiltrates (MC) and a cumulative inflammation score, generated by summing the two parameters. Scores in each group were compared using non-parametric statistical analysis. RESULTS: sPLA2 was localised to endothelium (EC), vascular smooth muscle (VSM), and mast cells (M) in all tissue sections. In RA and OA sections, staining was seen in both macrophage-like and fibroblast-like cells in the synovial lining layer (LL) and subsynovial lining layer (SLL). Perineural cells stained positively. Subintimal lymphoid aggregates (LA) were negative in all sections. The RA group showed significantly greater staining in extravascular synovial tissue (median 3.6, range 1.5-6.0) than the OA (median 1.95, range 0-5.3) or NA (median 0, range 0-5.9) groups (p < 0.05). LL staining was significantly higher in RA than both OA and NA sections (p < 0.05). The OA group showed a trend to higher staining scores than the NA group that did not reach significance. There was a significant correlation between the sPLA2 staining score and inflammation score within the RA patient group (p < 0.05). CONCLUSIONS: The synovium is a site of increased expression of sPLA2 antigen in both RA and OA relative to NA. Its presence in both fibroblast and macrophage-like cells in the LL and SLL of synovial tissue in RA and OA, but not NA, indicates that the enzyme is specifically induced in these regions in both conditions with expression in the LL being particularly characteristic of RA. The widespread expression of sPLA2 in synovium suggests it is likely to play a significant part in synovial pathology.
10446858 Selective expression of folate receptor beta and its possible role in methotrexate transpo 1999 Aug OBJECTIVE: To investigate the expression of folate receptors (FR) and reduced folate carrier (RFC) and determine their relevance to methotrexate (MTX) transport in synovial mononuclear cells (SMC) from patients with rheumatoid arthritis (RA). METHODS: Levels of FR and RFC messenger RNA (mRNA) were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in SMC from RA patients and peripheral blood mononuclear cells from healthy donors. Expression of FR-beta mRNA and protein was determined by Northern blot and Western blot analyses in RA SMC and monocyte/macrophage-lineage cells. FR-beta expression and folic acid binding capacity on the cell surface were examined by flow cytometric analysis and 3H-folic acid binding analysis. Studies of the inhibition of 3H-MTX uptake in the presence of unlabeled folic acid were performed to investigate the uptake of MTX through FR in RA SMC. RESULTS: RT-PCR, Northern blot, and Western blot analyses showed that FR-beta mRNA and protein were expressed selectively in activated monocytes and CD14+ RA SMC. These cells exhibited folic acid binding capacity. Furthermore, the FR-beta protein was shown to have folic acid binding capacity. Uptake of 3H-MTX through RA SMC was significantly inhibited in the presence of unlabeled folic acid. CONCLUSION: These results demonstrate that FR-beta expression is selectively elevated in RA synovial macrophages and suggest that MTX is transported through FR-beta in RA synovial macrophages. The findings suggest that folate antagonists with higher affinity for FR-beta would be useful in the treatment of RA.
10439120 Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fl 1999 Jun OBJECTIVE: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). METHODS: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. RESULTS: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p < 0.0001, p < 0.0001), and correlated with ESR in all arthritis (r = 0.658, p < 0.0001, r = 0.404, p < 0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727, p < 0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p < 0.01, p < 0.0001, p < 0.001) than those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. CONCLUSION: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA.
11187194 [Myalgia and high sedimentation rate in adults]. 2000 Nov 20 The polymyalgic syndrome may be the presenting clinical feature for several diseases such as polymyalgia rheumatica, temporal arteritis, malignancy, rheumatoid arthritis, virus infections, connective tissue diseases, and myositis. In this review we present the various diagnostic options seen from a rheumatological point of view, with emphasis on polymyalgia rheumatica, temporal arteritis and the paraneoplastic syndrome. We are of the opinion that polymyalgia rheumatica is overdiagnosed in general practice, and steroid treatment may delay diagnosis and treatment of other differential diagnosis presenting as the polymyalgic syndrome. Several recently published Norwegian epidemiological studies offer new information on various aspects of the polymyalgic syndrome, which will be discussed.
9916487 [Rheumatoid nodule diagnosed by thoracoscopy using flexible fiberoptic bronchoscope]. 1998 Nov A 51-year-old man had been treated at a nearby hospital since 1993 for rheumatoid arthritis. Right pectoralgia developed in December 1994, and the patient consulted a nearby hospital, which detected right pleural effusion retention was pointed out on chest x-ray films. The patient was referred and admitted to our hospital. Rheumatic pleurisy was suspected because of a high serum rheumatoid factor(RF)level and high RF and high rheumatoid arthritis hemagglutination levels in the pleural effusion. However, due to a high adenosine deaminase level in the pleural effusion tuberculous pleurisy could not be ruled out. After drainage through a trocar catheter, the thoracic cavity was examined by thoracoscopy through the site of catheter insertion. As a result, sporadic bluish white nodular lesions were observed on the pleura. Granuloma formations presenting a palisade arrangement of giant cells were also observed, and pathologically diagnosed as rheumatoid nodules, thus providing the basis for a diagnosis of rheumatic pleurisy. Treatment with an increased dose of prednisolone achieved a rapid remission of the pleural effusion. Our experience underscored the usefulness of thoracoscopy as a means diagnosing of rheumatic pleurisy.
10852976 Fas-associated death domain protein is a Fas-mediated apoptosis modulator in synoviocytes. 2000 May OBJECTIVE: To understand the intracellular regulatory mechanisms in Fas-mediated apoptosis of synoviocytes, we examined the involvement of caspases [caspase-1/ICE (interleukin-1beta converting enzyme), caspase-3/CPP32, and caspase-8/FLICE] and Fas-associated death domain protein (FADD) forming a death-inducing signalling complex (DISC) in Fas-mediated apoptosis of synoviocytes. METHODS: Synoviocytes were obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. The number of dead cells was counted after treatment with anti-Fas monoclonal antibody in the presence of caspase-1-, -3-, or -8-specific inhibitors. The involvement of caspases and FADD in Fas-mediated apoptosis of RA synoviocytes was examined by immunoblot and immunoprecipitation analyses. RESULTS: RA synoviocytes expressed high levels of caspase-3, caspase-8, and FADD compared with OA synoviocytes. Interestingly, Fas ligation activated caspase-8 and caspase-3 with the cleavage of poly(ADP-ribose) polymerase (PARP), corresponding to apoptosis of RA synoviocytes. Furthermore, specific inhibitors for caspase-3 and caspase-8 but not caspase-1 suppressed Fas-induced apoptosis of RA synoviocytes in a dose- and time-dependent manner. Caspase-8-specific inhibitor suppressed the activation of caspase-3 after Fas ligation on RA synoviocytes. Importantly, FADD was selectively recruited to the Fas death domain during Fas-mediated apoptosis of RA synoviocytes, consistent with sensitivity to the Fas-mediated apoptosis. CONCLUSION: Our findings suggest that Fas-mediated apoptosis in synoviocytes may be regulated at the level of recruitment of FADD to the DISC, subsequently leading to the activation of the FADD/caspase-8/caspase-3 signalling pathway.
11694430 MR imaging of inflammatory conditions of the ankle and foot. 2001 Aug Infection and noninfection inflammatory diseases commonly affect the foot and ankle; they have a significant impact on the cost of medical care and are a major source of referral for MR imaging evaluation. Recognition of the MR imaging appearance of the various manifestations of these disorders is important so that prompt and appropriate medical or surgical management can be instituted. This article emphasizes MR imaging of the most important diseases in this category, diabetic foot infection and the rheumatoid foot, but will also discuss manifestations in the foot and ankle of various other inflammatory diseases, such as gout and seronegative spondyloarthropathies.
10343541 Thrombin receptor mediated signals induce expressions of interleukin 6 and granulocyte col 1999 Jan OBJECTIVE: To clarify the mechanism of thrombin receptor mediated signal transduction and the induction of cytokines by thrombin stimulation in rheumatoid synovial fibroblasts. METHODS: Cytokines were measured by enzyme linked immunosorbent assay (ELISA) in the supernatants of cultured rheumatoid synovial fibroblasts stimulated by thrombin. To assess the mechanism of thrombin receptor mediated signal transduction in the rheumatoid synovial fibroblasts, electrophoretic mobility gel shift assay (EMSA), immunoglobulin kappa-chloramphenicol acetyltransferase (CAT) assay, and immunostaining for NF-kappa B subunit molecule was performed. RESULTS: Thrombin stimulation activated the inducible transcription factor NF-kappa B, and then induced subsequent expressions of interleukin 6 (IL6) and granulocyte colony stimulating factor (G-CSF) in the cells. CONCLUSION: Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-kappa B activation.
10517187 Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pan 1999 Aug The hypothesis of the present work was that the pannus tissue overlying the articular hard tissues has an aggressive phenotype and contains the newly discovered collagenase-3 and its endogenous inducers and activators. We therefore analyzed the eventual presence of collagenase-3 and its regulation at the pannus-cartilage junction. Collagenase-3 mRNA (in situ hybridization) and enzyme protein (ABC and immunofluorescence staining) were found in the pannocytes in the pannus-hard tissue junction. Inflammatory round cells associated with the critical interface contained TNF-alpha and IL-1beta. These cytokines induced collagenase-3 secretion in cultured rheumatoid synovial fibroblasts. Procollagenase-3 activators, stromelysin-1, 72 kDa type IV collagenase/gelatinase and membrane-type 1-MMP, were also found in the pannus-hard tissue junction. Active collagenase-3 was inhibited with alendronate (IC50 = 500-750 microM). Collagenase-3, due to its substrate profile and local synthesis in a milieu favoring its activation, might play a major role in the degradation of cartilage type II and bone type I collagens. Alendronate, at concentrations attainable in vivo, is able to inhibit collagenase-3. This might offer an option to control collagenase-3-mediated tissue destruction in rheumatoid arthritis.