Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes.


:Inadequate apoptosis may contribute to the synovial hyperplasia associated with rheumatoid arthritis (RA). The Fas-associated death domain protein (FADD)-like interleukin (IL)-1beta-converting enzyme (FLICE)-inhibitory protein (FLIP), which is an apoptotic inhibitor, has been implicated in the resistance to Fas-mediated apoptosis of synoviocytes. This study investigated whether hydroxychloroquine (HCQ), an anti-rheumatic drug, induces the apoptosis of rheumatoid synoviocytes, and modulates the expression of FLIP. Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and were cultured with various concentrations of HCQ in the presence or absence of the IgM anti-Fas monoclonal antibodies (mAb) (CH11). Treatment with HCQ, ranging from 1 to 100 microM, induced the apoptosis of FLS in a dose- and time-dependent manner. The increase in synoviocytes apoptosis by HCQ was associated with caspase-3 activation. A combined treatment of HCQ and anti-Fas mAb increased FLS apoptosis and caspase-3 activity synergistically, compared with either anti-Fas mAb or HCQ alone. The Fas expression level in the FLS was not increased by the HCQ treatment, while the FLIP mRNA and protein levels were decreased rapidly by the HCQ treatment. Moreover, time kinetics analysis revealed that the decreased expression of FLIP by HCQ preceded the apoptotic event that was triggered by HCQ plus anti-Fas mAb. Taken together, HCQ increases the apoptosis of rheumatoid synoviocytes by activating caspase-3, and also sensitizes rheumatoid synoviocytes to Fas-mediated apoptosis. Our data suggest that HCQ may exert its anti-rheumatic effect in rheumatoid joints through these mechanisms.


Clin Exp Immunol


Kim WU,Yoo SA,Min SY,Park SH,Koh HS,Song SW,Cho CS




Has Abstract


2006-06-01 00:00:00














  • Eosinophil involvement in rheumatoid arthritis as reflected by elevated serum levels of eosinophil cationic protein.

    abstract::Circulating levels of eosinophil cationic protein (ECP), an eosinophil specific granule protein, and numbers of peripheral eosinophils were determined in 42 patients with rheumatoid arthritis. At the time of the investigation the patients were without drug treatment. They had normal blood counts of eosinophils but on ...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Hällgren R,Feltelius N,Svenson K,Venge P

    更新日期:1985-03-01 00:00:00

  • Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H.

    abstract::Factor H is an abundant plasma glycoprotein that plays a critical role in the regulation of the complement system in plasma and in the protection of host cells and tissues from damage by complement activation. Several recent studies have described the association of genetic variations of the complement factor H gene (...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章,评审


    authors: de Córdoba SR,de Jorge EG

    更新日期:2008-01-01 00:00:00

  • Nickel-induced proliferation of both memory and naive T cells in patch test-negative individuals.

    abstract::Lymphocyte transformation test has often been used as an in vitro test for nickel allergy. We have previously demonstrated the presence of nickel-reactive T cells in individuals with no history of allergic disease and with a negative patch test towards NiSO4. In this study, we show that this proliferative response was...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Lisby S,Hansen LH,Menn T,Baadsgaard O

    更新日期:1999-08-01 00:00:00

  • Soluble complement receptor type 1 (sCR1) in chronic liver diseases: serum levels at different stages of liver diseases.

    abstract::Complement receptor type 1 (CR1) is an integral membrane protein of many haematopoietic cells and plays an important role in the clearance of complement-associated immune complexes, favouring their transport to liver and spleen macrophages. A small amount of soluble CR1 (sCR1) is also found in plasma and might origina...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Di Bona D,Montalto G,Clemenza L,Bascone F,Accardo P,Bellavia D,Craxì A,Brai M

    更新日期:1998-10-01 00:00:00

  • Different inflammatory cell pattern and macrophage phenotype in chronic obstructive pulmonary disease patients, smokers and non-smokers.

    abstract::Smokers exhibit airway inflammation and increased number of alveolar macrophages (AM), but not all develop chronic obstructive pulmonary disease (COPD). We hypothesized that AMs in COPD patients have an altered functional capacity mirrored in a different phenotype. Sixteen steroid-naive COPD patients [forced expirator...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Löfdahl JM,Wahlström J,Sköld CM

    更新日期:2006-09-01 00:00:00

  • Kinetics of interaction of immune complexes with complement receptors on human blood cells: modification of complexes during interaction with red cells.

    abstract::Antigen-antibody complexes, composed of 125I-BSA and guinea-pig or rabbit antibody, were incubated at 37 degrees C with human blood cells suspended in autologous serum and kinetics of binding analysed. When purified polymorphonuclear (PMN) or mononuclear cells (MNC) were studied, maximum binding was observed within 8 ...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Medof ME,Prince GM,Oger JJ

    更新日期:1982-06-01 00:00:00

  • Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

    abstract::The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Harris DT,Badowski M,Balamurugan A,Yang OO

    更新日期:2013-12-01 00:00:00

  • A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients.

    abstract::Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnos...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Pazhouhandeh M,Sahraian MA,Siadat SD,Fateh A,Vaziri F,Tabrizi F,Ajorloo F,Arshadi AK,Fatemi E,Piri Gavgani S,Mahboudi F,Rahimi Jamnani F

    更新日期:2018-04-01 00:00:00

  • Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes.

    abstract::Intestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demons...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Okazawa A,Kanai T,Nakamaru K,Sato T,Inoue N,Ogata H,Iwao Y,Ikeda M,Kawamura T,Makita S,Uraushihara K,Okamoto R,Yamazaki M,Kurimoto M,Ishii H,Watanabe M,Hibi T

    更新日期:2004-05-01 00:00:00

  • Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection.

    abstract::The controlled induction of haemoxygenase-1 (HO-1), an enzyme that catabolizes haem, has been shown to reduce haem, preventing pathologies associated with haem toxicity. The hemoglobin genotype HbAS confers reduced susceptibility to severe complications of malaria by a mechanism that is not well understood. Using a lo...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Ademolue TW,Amodu OK,Awandare GA

    更新日期:2017-05-01 00:00:00

  • IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans.

    abstract::We examined the role of IL-12 in host resistance to Cryptococcus neoformans using a murine model of pulmonary and disseminated infection. In this model, mice were infected intratracheally with viable yeast cells. Mice untreated with IL-12 allowed an uncontrolled multiplication of yeast cells in the lung with infiltrat...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Kawakami K,Tohyama M,Xie Q,Saito A

    更新日期:1996-05-01 00:00:00

  • The distribution of a specific HLA-B27-associated cell surface component on the tissues of patients with ankylosing spondylitis.

    abstract::In this paper, we report the presence on Epstein-Barr virus-transformed lymphoblastoid cell lines on platelets and on fibroblasts of an HLA-B27-associated cell surface complex (antigenically related to some antigens of Klebsiella K43 and K21) which is identical to or cross-reactive with the determinant present on the ...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Alexander K,Edwards C,Misko IS,Geczy AF,Bashir HV,Edmonds JP

    更新日期:1981-07-01 00:00:00

  • Lack of activity of 15-epi-lipoxin A₄ on FPR2/ALX and CysLT1 receptors in interleukin-8-driven human neutrophil function.

    abstract::Neutrophil recruitment and survival are important control points in the development and resolution of inflammatory processes. 15-epi-lipoxin (LX)A interaction with formyl peptide receptor 2 (FPR2)/ALX receptor is suggested to enhance anti-inflammatory neutrophil functions and mediate resolution of airway inflammation....

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Planagumà A,Domenech T,Jover I,Ramos I,Sentellas S,Malhotra R,Miralpeix M

    更新日期:2013-08-01 00:00:00

  • Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery.

    abstract::The systemic inflammatory response is a challenge in the management of paediatric patients undergoing cardiac surgery. Although multi-factorial, a contribution by the lectin pathway of complement activation has been postulated. We therefore investigated the changes in serum levels of mannose binding lectin (MBL) and a...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Pągowska-Klimek I,Świerzko AS,Michalski M,Głowacka E,Szala-Poździej A,Sokołowska A,Moll M,Krajewski WR,Romak J,Cedzyński M

    更新日期:2016-05-01 00:00:00

  • Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels.

    abstract::CD4+CD25+ T regulatory cells may play a role in the different clinical presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T cell responses. Peripheral CD4+CD25+ T cells from chronic HCV carriers with normal and abnormal alanine aminotransferase (ALT) were analysed for specificity and effect...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Bolacchi F,Sinistro A,Ciaprini C,Demin F,Capozzi M,Carducci FC,Drapeau CM,Rocchi G,Bergamini A

    更新日期:2006-05-01 00:00:00

  • Nicotine exposure alters in vivo human responses to endotoxin.

    abstract::The alpha 7 nicotinic receptor is reportedly a key element in the cholinergic anti-inflammatory pathway. Because a prototypical ligand for this receptor is nicotine, we studied the in vivo human response to bacterial endotoxin or lipopolysaccharide (LPS) in the context of nicotine or placebo pretreatment. Twelve adult...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章,随机对照试验


    authors: Wittebole X,Hahm S,Coyle SM,Kumar A,Calvano SE,Lowry SF

    更新日期:2007-01-01 00:00:00

  • Plasma membrane association of primary biliary cirrhosis mitochondrial marker antigen M2.

    abstract::Antibody reactivity against the 'mitochondrial M2 antigen' was determined in sera from 10 patients with primary biliary cirrhosis (PBC), using Western blotting after SDS-PAGE separation of rat liver mitochondria (RLM) and plasma membrane proteins. The molecular weights of the major M2 antigens in rat liver mitochondri...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Sundin U,Sundqvist KG

    更新日期:1991-03-01 00:00:00

  • E-rosette forming cell numbers in the blood of human renal allograft recipients.

    abstract::The incidence of circulating T lymphocytes (ET-RFC) and a sub-population of T lymphocytes (EE-RFC) were monitored in the blood of seventy-one cadaver renal allograft recipients for the first 2 months after transplantation. In patients with uneventful post-operative courses, the incidence of both ET-RFC and EE-RFC fell...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Kelly GE,Sheil AG

    更新日期:1977-03-01 00:00:00

  • The effect of interleukin-10 and of interleukin-12 on the in vitro production of anti-double-stranded DNA antibodies from patients with systemic lupus erythematosus.

    abstract::IL-10 and IL-12 are cytokines which are important in regulating immune responses. Plasma levels of IL-10 and autoantibodies against double-stranded DNA (dsDNA) often mirror disease activity in patients with SLE. IL-12 secretion from SLE patients' blood mononuclear cells also correlates with disease activity, but has a...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Tyrrell-Price J,Lydyard PM,Isenberg DA

    更新日期:2001-04-01 00:00:00

  • Variable effects of cyclophosphamide in rodent models of experimental allergic encephalomyelitis.

    abstract::In this study, we have evaluated the effects of cyclophosphamide on the development of experimental allergic encephalomyelitis (EAE) in four EAE rodent models: monophasic EAE in Lewis rats, protracted relapsing (PR)-EAE in DA rats, myelin oligodendrocyte protein (MOG)-induced EAE in C57Bl/6 mice and proteolipid protei...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Mangano K,Nicoletti A,Patti F,Donia M,Malaguarnera L,Signorelli S,Magro G,Muzio V,Greco B,Zaratin P,Meroni P,Zappia M,Nicoletti F

    更新日期:2010-02-01 00:00:00

  • Antisera to human IgE can also recognize IgA and IgM molecules as produced by selected B lymphoblastoid cell lines.

    abstract::A series of polyclonal and monoclonal anti-human IgE sera reacted with a panel of 11 selected IgA and IgM producing B lymphoblastoid cell lines (BLCLs) in cytoplasmic fluorescence, ELISA and immunoprecipitation assays. The reactions were discordant between the BLCLs and the individual antisera. The panel of 11 BLCLs w...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Hendriks RW,Thompson A,Kraakman ME,Drayer AL,Schuurman RK

    更新日期:1988-11-01 00:00:00

  • Clearance of red cells by monoclonal IgG3 anti-D in vivo is affected by the VF polymorphism of Fcgamma RIIIa (CD16).

    abstract::Human red cells (RBC) coated with IgG anti-D are cleared from the circulation to the spleen by macrophages which express IgG receptors (Fcgamma R). Polymorphisms of Fcgamma RIIa and Fcgamma RIIIa affect IgG binding in vitro, and may alter the efficiency of clearance of immune complexes in vivo. In a RBC clearance stud...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Kumpel BM,De Haas M,Koene HR,Van De Winkel JG,Goodrick MJ

    更新日期:2003-04-01 00:00:00

  • Expression of anticardiolipin cofactor, human beta 2-glycoprotein I, by a recombinant baculovirus/insect cell system.

    abstract::A full-length cDNA coding a human beta 2-glycoprotein I (beta 2-GPI) was introduced into the baculovirus genome to construct a recombinant baculovirus. Spodoptera frugiperda (Sf9) cells were infected with the recombinant baculovirus. A protein (mol. wt 43,000) reactive with anti-beta 2-GPI antisera was produced in the...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Igarashi M,Matsuura E,Igarashi Y,Nagae H,Matsuura Y,Ichikawa K,Yasuda T,Voelker DR,Koike T

    更新日期:1993-07-01 00:00:00

  • T cell subsets in leprosy lesions: in situ characterization using monoclonal antibodies.

    abstract::Cryostat sections of dermal lesions from 30 untreated leprosy patients were studied by indirect immunofluorescence using monoclonal antibodies defining T cell subsets and Ia like antigens. Most lymphocytes in leprosy lesions were positive for OKT3 and Ia like antigens indicating thereby the presence of activated T cel...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Narayanan RB,Bhutani LK,Sharma AK,Nath I

    更新日期:1983-03-01 00:00:00

  • Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region.

    abstract::To formulate a 'logic' for how a single immunoglobulin variable region gene generates antibodies with different antigen specificity and polyreactivity, we analysed chimeric antibodies produced in transgenic mice carrying the germ-line human V3-23 gene, multiple diversity (D) and joining (J) gene segments. Hybridomas p...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Mageed RA,Harmer IJ,Wynn SL,Moyes SP,Maziak BB,Brüggemann M,MacKworth-Young CG

    更新日期:2001-01-01 00:00:00

  • Induction of immunological memory in the skin. Role of local T cell retention.

    abstract::Using an experimental contact sensitivity model in guinea-pigs, evidence is presented that hapten (DNCB or oxazolone) specific T lymphocytes may persist for several months in previous sites of inflammation. Immunological memory, revealed by accelerated contact skin reactions upon retesting with the hapten, was limited...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Scheper RJ,von Blomberg M,Boerrigter GH,Bruynzeel D,van Dinther A,Vos A

    更新日期:1983-01-01 00:00:00

  • Generation and functional analysis of T cell lines and clones specific for schistosomula released products (SRP-A).

    abstract::Antigens present in the products released by the larval stage of schistosome (SRP-A) were shown to induce a strong cytotoxic and protective IgE response both in the rat and the monkey. T cell lines and clones specific for SRP-A or 26 kD antigens which are the main target of the cytotoxic IgE have been derived. The pas...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Damonneville M,Velge F,Verwaerde C,Pestel J,Auriault C,Capron A

    更新日期:1987-08-01 00:00:00

  • Decrease of peripheral large granular lymphocytes in Graves' disease.

    abstract::Peripheral large granular lymphocytes (LGL) were enumerated in normal subjects and patients with autoimmune thyroid diseases. In normal subjects, the percentage of LGL was significantly lower in women (mean +/- s.d., 17.0 +/- 3.6%; n = 35; P less than 0.05) than in men (19.5 +/- 5.3%; n = 20). In untreated patients wi...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Iwatani Y,Amino N,Kabutomori O,Mori H,Tamaki H,Motoi S,Izumiguchi Y,Miyai K

    更新日期:1984-01-01 00:00:00

  • Reduced blood BDCA-2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus.

    abstract::Type 1 IFN is thought to be implicated in the autoimmune process of SLE. Plasmacytoid dendric cells (DC), which are natural IFN-alpha producing cells, play a pivotal epipathogenic role in SLE. The present study was undertaken to investigate the phenotypic characteristics of peripheral blood DC in SLE patients in compa...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Migita K,Miyashita T,Maeda Y,Kimura H,Nakamura M,Yatsuhashi H,Ishibashi H,Eguchi K

    更新日期:2005-10-01 00:00:00

  • Complement membrane attack is required for endplate damage and clinical disease in passive experimental myasthenia gravis in Lewis rats.

    abstract::Myasthenia gravis (MG) is a debilitating and potentially fatal neuromuscular disease characterized by the generation of autoantibodies reactive with nicotinic acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular endplate with resultant failure of neuromuscular transmission. A role for compleme...

    journal_title:Clinical and experimental immunology

    pub_type: 杂志文章


    authors: Chamberlain-Banoub J,Neal JW,Mizuno M,Harris CL,Morgan BP

    更新日期:2006-11-01 00:00:00