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1.
In mice and humans two distinct CD4+ helper T cells, known as Th1 and Th2 are identified. They are characterized by the different
cytokine milleau they induce. The balance between Th1 and Th2 responses is thought to be decisive for the initiation and course
of some autoimmune disorders, as well as for the outcome of infectious processes. In the present study the development of
Candida alibcans infection in mice with adjuvant-induced arthritis was investigated. An impaired host resistance against C. alibcans in arthritic mice was registered when the inoculation was done during the early and the established phases of arthritis.
In contrast, the slight elevation of the number of survivors was detected when the infection was induced at the peak of inflammation.
These data correlated with the changes of serum TNF-α level and delayed type hypersensitivity (DTH) toC. alibcans.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
2.
Rikard Holmdahl Carina Vingsbo-Lundberg Niklas Nordquist Peter Olofsson Mats Sundvall Tore Saxne Ulf Pettersson 《Journal of Experimental Animal Science》2000,41(1-2)
This study was specifically designed to analyse the genetic control of the chronic disease course for the development of arthritis. Arthritis models with a chronic erosive arthritis are collagen induced arthritis induced with homologous collagen in oil but also arthritis induced with certain non-immunogenic adjuvants such as pristane and avridine. In the presently described experiment we have used pristane induced arthritis. A single injection of 150 μl pristane induces severe chronic arthritis in DA rats. The disease mimics rheumatoid arthritis in many aspects such as the chronic disease course, an erosive inflammation of peripheral joints, symmetric involvement of the joints and the development of rheumatoid factors. To determine the genetic contribution we have used a number of inbred, recombinant inbred and congenic strains as well as specifically designed segregating crosses. An influence by the MHC region (designated Pia1 locus) on the chronic disease course was determined through the uses of MHC congenic LEW strains in which the RT1-f haplotype conferred highest susceptibility. To map genes outside of MHC we used an F2 cross between the highly susceptible DA and the resistant E3 strains. Loci exclusively associated with different phenotypes of the disease could be identified:
- Arthritis onset (Pia2 and Pia3).
- Severity and joint erosions (Pia4).
- Chronicity (Pia5 and Pia6) and Pia1 (determined from MHC congenic (strains)
3.
《MABS-AUSTIN》2013,5(5)
mAbs’ September/October 2009 issue highlights the promise and challenges of antibody therapeutics development. Representing promise, our mini-review series on novel antibodies currently undergoing regulatory review or recently approved continues in this issue. Previously published articles include mini-reviews of denosumab and ustekinumab (May/June 2009 issue) and ofatumumab (July/August 2009 issue). The September/October issue features articles on golimumab, tocilizumab and motavizumab. The mini-reviews present overviews of the completed and on-going clinical studies of these molecules. Anti-TNFα golimumab was approved in April 2009 by both the US Food and Drug Administration (FDA) and Health Canada as a treatment for rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis; anti-IL6R tocilizumab is approved in Japan and the European Union (EU), and is currently undergoing FDA review as a treatment for RA. The juxtaposition of these two mini-reviews provides an opportunity to easily compare summaries of the available clinical results. Future issues of mAbs will include mini-reviews of catumaxomab, canakinumab and raxibacumab, as well as any additional antibodies that enter regulatory review in 2009 and beyond. 相似文献
4.
5.
Ramzi Nehmar Louis Fauconnier Jose Alves-Filho Dieudonnée Togbe Aurore DeCauwer Seiamak Bahram Marc Le Bert Bernhard Ryffel Philippe Georgel 《Journal of cellular and molecular medicine》2021,25(10):4721-4731
The aryl hydrocarbon receptor (AHR) controls several inflammatory and metabolic pathways involved in various diseases, including the development of arthritis. Here, we investigated the role of AHR activation in IL-22-dependent acute arthritis using the K/BxN serum transfer model. We observed an overall reduction of cytokine expression in Ahr-deficient mice, along with decreased signs of joint inflammation. Conversely, we report worsened arthritis symptoms in Il-22 deficient mice. Pharmacological stimulation of AHR with the agonist VAG539, as well as injection of recombinant IL-22, given prior arthritogenic triggering, attenuated inflammation and reduced joint destruction. The protective effect of VAG539 was abrogated in Il-22 deficient mice. Finally, conditional Ahr depletion of Rorc-expressing cells was sufficient to attenuate arthritis, thereby uncovering a previously unsuspected role of AHR in type 3 innate lymphoid cells during acute arthritis. 相似文献
6.
Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes.
High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however,
IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been
observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-α, IL-1, and receptor activator
of NF-κB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-α in inducing cytokine expression and joint
damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17
has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17
cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which
elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy. 相似文献
7.
Rat adjuvant arthritis (AA) is an animal model of rheumatoid arthritis in which pannus formation and destruction of joints occur after immunization with complete Freund's adjuvant. Neovascularization is present within the synovium and may be critical for pannus growth. In this study the effects of a novel angiogenesis inhibitor, AGM-1470, on AA were evaluated. Lewis rats were immunized with CFA to induce arthritis. AGM-1470 treatment was initiated prior to arthritis onset (preventative protocol) or administered to rats with established disease (suppressive protocol). The severity of synovitis and the immunologic status of all rats were then evaluated. Using clinical and radiographic criteria, AGM-1470 significantly reduced arthritis incidence (preventative protocol) (P < 0.01) and disease severity (both protocols, P < 0.001, compared to controls) without affecting T cell function in vitro or phenotype in vivo. Additionally, histologic sections from control rats revealed marked pannus formation, destruction of bone/cartilage, and neovascularization. These findings were absent in AGM-1470-treated rats. AGM-1470 may offer a new treatment option for rheumatoid arthritis and other angiogenesis-dependent diseases. 相似文献
8.
Hinks A Martin P Flynn E Eyre S Packham J;Childhood Arthritis Prospective Study-CAPS;BSPAR Study Group Barton A Worthington J Thomson W 《Arthritis research & therapy》2011,13(1):R12
Introduction
Juvenile idiopathic arthritis (JIA) is an umbrella term for all chronic childhood arthropathies and can be divided into seven subtypes. It includes the enthesitis related arthritis (ERA) subtype which displays symptoms similar to ankylosing spondylitis (AS) and juvenile-onset psoriatic arthritis which has similarities to psoriatic arthritis (PsA) and psoriasis (Ps). We, therefore, hypothesized that two well-established susceptibility loci for AS and Ps, ERAP1 and IL23R, could also confer susceptibility to these JIA subtypes. 相似文献9.
Urvater JA McAdam SN Loehrke JH Allen TM Moran JL Rowell TJ Rojo S López de Castro JA Taurog JD Watkins DI 《Immunogenetics》2000,51(4-5):314-325
The human major histocompatibility complex (MHC) class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies. Rodents that express HLA-B27 develop spondyloarthropathies, implicating HLA-B27 in the etiology of these disorders. To determine whether an HLA-B27-like molecule was associated with spondyloarthropathies
in nonhuman primates, we analyzed the MHC class I cDNAs expressed in a cohort of rhesus macaques that developed reactive arthritis
after an outbreak of shigellosis. We identified several cDNAs with only limited sequence similarity to HLA-B27. Interestingly, one of these MHC molecules had a B pocket identical to that of HLA-B39. Pool sequencing of radiolabeled peptides
bound by this molecule demonstrated that, like HLA-B27 and HLA-B39, it could bind peptides with arginine at the second position.
However, extensive analysis of the MHC class I molecules in this cohort revealed no statistically significant association
between any particular MHC class I allele and susceptibility to reactive arthritis. Furthermore, none of the rhesus MHC class I
molecules bore a strong resemblance to HLA-B27, indicating that reactive arthritis can develop in this animal model in the
absence of an HLA-B27-like molecule. Surprisingly, there was a statistically significant association between the rhesus macaque
MHC A locus allele, Mamu-A*12, and the absence of reactive arthritis following Shigella infection.
Received: 26 July 1999 / Revised: 28 December 1999 相似文献
10.
Kyoko Wakamatsu Toshihiro Nanki Nobuyuki Miyasaka Kazuo Umezawa Tetsuo Kubota 《Arthritis research & therapy》2005,7(6):R1348
A small cell-permeable compound, dehydroxymethylepoxyquinomicin (DHMEQ), does not inhibit phosphorylation and degradation
of IκB (inhibitor of nuclear factor-κB [NF-κB]) but selectively inhibits nuclear translocation of activated NF-κB. This study
aimed to demonstrate the antiarthritic effect of this novel inhibitor of the NF-κB pathway in vivo in a murine arthritis model and in vitro in human synovial cells. Collagen-induced arthritis was induced in mice, and after onset of arthritis the mice were treated
with DHMEQ (5 mg/kg body weight per day). Using fibroblast-like synoviocyte (FLS) cell lines established from patients with
rheumatoid arthritis (RA), NF-κB activity was examined by electrophoretic mobility shift assays. The expression of molecules
involved in RA pathogenesis was determined by RT-PCR, ELISA, and flow cytometry. The proliferative activity of the cells was
estimated with tritiated thymidine incorporation. After 14 days of treatment with DHMEQ, mice with collagen-induced arthritis
exhibited decreased severity of arthritis, based on the degree of paw swelling, the number of swollen joints, and radiographic
and histopathologic scores, compared with the control mice treated with vehicle alone. In RA FLS stimulated with tumor necrosis
factor-α, activities of NF-κB components p65 and p50 were inhibited by DHMEQ, leading to suppressed expression of the key
inflammatory cytokine IL-6, CC chemokine ligand-2 and -5, matrix metalloproteinase-3, intercellular adhesion molecule-1, and
vascular cell adhesion molecule-1. The proliferative activity of the cells was also suppressed. This is the first demonstration
of an inhibitor of NF-κB nuclear translocation exhibiting a therapeutic effect on established murine arthritis, and suppression
of inflammatory mediators in FLS was thought to be among the mechanisms underlying such an effect. 相似文献
11.
Collagen-induced arthritis (CIA) is a rodent arthritis model in which immunization with heterologous type II collagen induces an inflammatory polyarthritis. Susceptibility to the disease is mediated by major histocompatibility complex (MHC) genes as well as genes at other loci. Previous studies of the SWR/J mouse strain, which is resistant to CIA despite bearing the susceptible H-2
q
haplotype, have suggested that this resistance is the result of a deletion of T-cell receptor (Tcr) Vb gene segments which is carried by this strain. Other studies have implicated a deficiency in complement component C5 as the cause for the resistance. In order to assess the relative importance of these two genes in susceptibility to CIA, and to provide an estimate of the number of independent genes involved in the disease, we analyzed 196 F2 progeny of a (DBA/1 × SWR/J) cross for arthritis susceptibility, and expression of both C5 and Tcr genes. Thirty of the F2 progeny developed arthritis. All of the arthritic mice had at least one copy of the wild-type C5 allele, while the Tcr-Vb haplotypes were distributed in Mendelian fashion. These results demonstrate that C5 sufficiency is an absolute requirement for CIA, but that Tcr-Vb genes located within the SWR deletion have little influence. Genetic analysis of the incidence rate suggests that there is polygenic control of susceptibility to CIA and that in addition to H-2, 5–6 other independent loci (including C5) may be involved. 相似文献
12.
Abstract: As the arboreal ape, Pongo, has an unusual ground ambulation adaptation, it was of interest to assess the impact of Pongo gait on patterns of arthritis. While osteoarthritis was not identified in Pongo, 11% of individual skeletons were afflicted with an inflammatory, erosive arthritis. The presence of sacroiliac involvement and the nature and distribution of erosive lesions allowed definitive diagnosis of spondyloarthropathy. Character, distribution, and radiologic appearance revealed a picture distinguishable from spondyloarthropathy in other primates. 相似文献
13.
Weight loss is typically found during severe infections, e.g. septic arthritis. The aim of our study was to evaluate the role
of leptin, regulator of food intake and energy expenditure, for the development of Staphylococcus aureus-triggered arthritis. Leptin production was found to be decreased during murine S. aureus-induced arthritis. Treatment with recombinant leptin neither restored the basal leptin levels nor affected the weight loss
during the disease, but it significantly decreased the severity of septic arthritis. Exogenous leptin did not affect the staphylococcal
load as measured in blood, joints and kidneys. Preceding the effects on joint manifestations, serum levels of interleukin-6
decreased in leptin-treated mice. In conclusion, the treatment with recombinant leptin reduced both the severity of joint
manifestations in S.aureus-induced arthritis and the inflammatory response, as measured by serum IL-6 levels, without affecting the survival of bacteria
in vivo. 相似文献
14.
15.
G. E. Osman Mark C. Hannibal Jon P. Anderson Stephen R. Lasky Warren C. Ladiges Leroy Hood 《Immunogenetics》1999,49(10):851-859
Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced
arthritis (CIA) in mice is an autoimmune disease model of rheumatoid arthritis. Susceptibility to CIA in mice is linked to
genes of the major histocompatibility complex (MHC). CD4+ T cells that express the T-cell receptor (TCR) Tcra-V11.1 and/or Tcrb-V8.2 play a key role in the pathogenesis of arthritis in the DBA/1 mouse (H2
q
). We identified an inbred mouse strain, FVB/NJ (H2
q
), that is resistant to arthritis induction and exhibits a genomic deletion of certain Tcrb-V gene segments. We report a novel polymerase chain reaction-based method for the rapid identification of new mouse strains
that exhibit germline Tcrb-V gene deletions. We mapped for the first time both the 5′ and 3′ breakpoints of the Tcrb-V deletion in the FVB/NJ, SWR, SJL, C57L, and C57BR strains to within 1.1 kilobases. Since there is an association between
a particular Tcra-V allele (Tcra-V11.1
d
) and arthritis susceptibility in H2
q
mouse strains, we examined the allelic polymorphisms of the Tcra-V11 gene subfamily members between the arthritis-susceptible DBA/1 mouse and the arthritis-resistant FVB/NJ mouse strain. The
amino acid sequences of the Tcra-V11.1 alleles differ at two positions (codons 18 and 68). Therefore, the resistance of FVB/NJ mouse to arthritis induction may
be due in part to Tcra-V11.1 coding sequence polymorphism and Tcrb-V8.2 gene segment deletion, as we have recently demonstrated in the case of SWR mouse strain.
Received: 12 January 1999 / Revised: 17 March 1999 相似文献
16.
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of febrile peritonitis,
pleuritis and synovitis. Arthritis is a common and important feature of FMF. The clinical spectrum of arthritis in 71 FMF
patients was retrospectively investigated. Mutations in the familial Mediterranean (MEFV) gene were screened. Unlike the previous reports on arthritis of FMF, most of the FMF patients (59%) in this study had symmetric
two-joint arthritis whereas monoarticular, oligoarticular and polyarticular arthritis was presented in 20, 8 and 10% of the
patients, respectively. Knees were affected in 45 (63%) patients, ankles in 30 (42%), elbows in 11 (15%), wrists in 12 (17%),
hips in 12 (17%), small joints of the hands 7 (10%), small joints of the feet 2 (3%) and sacroiliac in 1 (1%). Destruction
of the hip was observed in 2 (3%) patients and required hip replacement. Amyloidosis developed in 2 (3%) of our patients.
Mutations in the MEFV gene were identified in 50 (71%) patients and the most dominant mutation detected was M694V (64%). Since FMF can be diagnosed
by a simple DNA mutation analysis, all arthritis patients of certain origins (Arabs, Turks, Armenians and Jews) should be
tested for FMF in order to prevent the complications (amyloidosis and protracted arthritis) by introducing colchicine which
is the treatment of choice for FMF. 相似文献
17.
Joint cartilage is attacked in both autoimmune inflammatory and osteoarthritic processes. Type IX collagen (CIX) is a protein
of importance for cartilage integrity and stability. In this study we have backcrossed a transgenic disruption of the col9a1 gene, which leads to an absence of CIX, into two different inbred mouse strains, DBA/1 and B10.Q. None of the CIX-deficient
mice developed observable clinical or microscopic osteoarthritis, but DBA/1 male mice had more pronounced enthesopathic arthritis,
the so-called stress-induced arthritis. Both DBA/1 and B10.Q strains are susceptible to the induction of collagen-induced
arthritis, and CIX deficiency in both strains led to the development of a more severe arthritis than in the controls. Induction
of arthritis with monoclonal antibodies against type II collagen (CII) led to an earlier arthritis in the paws that also involved
the knee joints. The antibodies used, which were specific for the J1 and the C1I epitopes of CII, initiate their arthritogenic attack by binding to cartilage. The C1I-specific antibodies bound to cartilage better in CIX-deficient mice than in wild-type animals, demonstrating that the lack
of CIX in cartilage leads to an increased accessibility of structures for antibody binding and thus making the joints more
vulnerable to inflammatory attack. These findings accentuate the importance of cartilage stability; cartilage disrupted as
a result of genetic disorders could be more accessible and vulnerable to an autoimmune attack by pathogenic antibodies. 相似文献
18.
Indoleamine 2,3-dioxygenase (IDO) is one of the initial and rate-limiting enzymes involved in the catabolism of the essential
amino acid tryptophan. In cultured cells, the induction of IDO leads to depletion of tryptophan and tryptophan starvation.
Recent studies suggest that modulation of tryptophan concentration via IDO plays a fundamental role in innate immune responses.
Induction of IDO by interferon-γ in macrophages and dendritic cells results in tryptophan depletion and suppresses the immune-mediated
activation of fibroblasts and T, B, and natural killer cells. To assess the role of IDO in collagen-induced arthritis (CIA),
a model of rheumatoid arthritis characterized by a primarily Th1-like immune response, activity of IDO was inhibited by 1-methyl-tryptophan
(1-MT) in vivo. The results showed significantly increased incidence and severity of CIA in mice treated with 1-MT. Activity of IDO, as
determined by measuring the levels of kynurenine/tryptophan ratio in the sera, was increased in the acute phase of arthritis
and was higher in collagen-immunized mice that did not develop arthritis. Treatment with 1-MT resulted in an enhanced cellular
and humoral immune response and a more dominant polarization to Th1 in mice with arthritis compared with vehicle-treated arthritic
mice. The results demonstrated that development of CIA was associated with increased IDO activity and enhanced tryptophan
catabolism in mice. Blocking IDO with 1-MT aggravated the severity of arthritis and enhanced the immune responses. These findings
suggest that IDO may play an important and novel role in the negative feedback of CIA and possibly in the pathogenesis of
rheumatoid arthritis. 相似文献
19.
L. Dai D.J. Lamb D.S. Leake M.L. Kus H.W. Jones C.J. Morris 《Free radical research》2013,47(6):479-486
The oxidative modification of human LDL has been implicated in atherosclerosis, but the mechanisms by which such modification occurs in vivo are not fully understood. In the present study, we have isolated LDL from knee-joint synovial fluid of patients with rheumatoid arthritis. We demonstrate that such LDL is oxidatively modified as evidenced by an increased negative charge, distorted particulate nature and more rapid degradation by cultured macrophages. These results indicate that formation of oxidised LDL is associated with the local inflammatory response. Because the cellular interactions in rheumatoid arthritis have analogies with those in atherogenesis, we suggest that the rheumatoid joint is a useful model of atherosclerosis in which the in vivo process of LDL oxidation may be readily studied. 相似文献
20.
Di Genaro MS Escudero ME Muñoz E Aguilera C Juarez A Scardapane L de Guzmán AM 《Folia microbiologica》1998,43(6):690-696
An animal model, hamster, was used for the study ofYersinia-induced arthritis. The development of arthritis, estimated by measuring the inflammation on hind paws after infection, was
correlated with the kinetics of the immune response. Hostological and immunofluorescence (IFI) studies and serum antibody
measurements were performed. Two inflammatory peaks were observed: an acute one on day 11 post-infection (p.i) and a chronic
one on days 26–35 p.i. Joint cultures were positive until day 14 p.i. IFI was used to demonstrate the deposit of bacterial
antigens in the joint. A persistent response of cellular extract-specific IgG antibodies was observed until day 94. Lipopolysaccharide-specific
IgG was statistically significant on day 26 p.i. Antibodies against bands 66 and 54 were observed by immunoblotting. Polyclonal
activation was detected during reactive arthritis. It is shown thatY. enterocolitica is arthritogenic in hamsters, immune mechanisms participating in the development of this disease. 相似文献