Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent developments in plasma lipoprotein and apolipoprotein research have been striking, but few studies have focused on the analysis of lipoproteins in synovial fluid (SF). SF contains small amounts of lipoproteins and apolipoproteins. The lipid concentration of normal human SF is extremely low and is in sharp contrast to the concentrations found in plasma. Little is known about the lipids in pathological SF, but studies have noted increased cholesterol and lipoprotein content in rheumatoid arthritis (RA) SF ranging from 40% to 60% of the total plasma lipoproteins. Recently apolipoproteins AI, B and E have also been found to be in increased amounts in RA SF. Several theories have been proposed to account for the increased presence of SF lipids in RA. Animal and human studies indicate the SF cholesterol, lipoproteins, and apolipoproteins may aggravate the inflammatory reaction within the synovial space. Research suggests an immunologic role for plasma lipoproteins on lymphocyte and monocytes in the blood and lymph. SF lipoproteins and apolipoproteins should be studied to define their actions within the synovial space.
Semin Arthritis Rheum 1993 Oct
PMID:Synovial fluid lipoproteins: review of current concepts and new directions. 826 11

Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.
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PMID:Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints. 1158 72

Hypochlorous acid (HOCl) is a potent oxidant, which is produced in vivo by activated phagocytes. This compound is an important antibacterial agent, but excessive or misplaced production has been implicated in a number of human diseases, including atherosclerosis, arthritis, and some cancers. Proteins are major targets for this oxidant, and such reaction results in side-chain modification, backbone fragmentation, and cross-linking. Despite a wealth of qualitative data for such reactions, little absolute kinetic data is available to rationalize the in vitro and in vivo data. In this study, absolute second-order rate constants for the reactions of HOCl with protein side chains, model compounds, and backbone amide (peptide) bonds have been determined at physiological pH values. The reactivity of HOCl with potential reactive sites in proteins is summarized by the series: Met (3.8 x 10(7) M(-1) x s(-1)) > Cys (3.0 x 10(7) M(-1) x s(-1)) >> cystine (1.6 x 10(5) M(-1) x s(-1)) approximately His (1.0 x 10(5) M(-1) x s(-1)) approximately alpha-amino (1.0 x 10(5) M(-1) x s(-1)) > Trp (1.1 x 10(4) M(-1) x s(-1)) > Lys (5.0 x 10(3) M(-1) x s(-1)) >> Tyr (44 M(-1) x s(-1)) approximately Arg (26 M(-1) x s(-1)) > backbone amides (10-10(-3) M(-1) x s(-1)) > Gln(0.03 M(-1) x s(-1)) approximately Asn (0.03 M(-1) x s(-1)). The rate constants for reaction of HOCl with backbone amides (peptide bonds) vary by 4 orders of magnitude with uncharged peptide bonds reacting more readily with HOCl than those in a charged environment. These kinetic parameters have been used in computer modeling of the reactions of HOCl with human serum albumin, apolipoprotein-A1 and free amino acids in plasma at different molar excesses. These models are useful tools for predicting, and reconciling, experimental data obtained in HOCl-induced oxidations and allow estimations to be made as to the flux of HOCl to which proteins are exposed in vivo.
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PMID:Absolute rate constants for the reaction of hypochlorous acid with protein side chains and peptide bonds. 1159 38

Stimulation of monocytes/macrophages after cell contact with preactivated T cells has been suggested to contribute to the excessive TNF-alpha production in rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-alpha production by peripheral-blood monocytes in vitro was investigated and found to be significantly lower in treated and untreated patients with RA than in healthy controls. This suppression was not due to a general deficiency of monocytes to respond, because responses to lipopolysaccharide were comparable in patients and controls. In agreement with the pivotal role of TNF-alpha in RA, T cell-dependent induction of TNF-alpha in synovial macrophages was fivefold to tenfold higher than in peripheral-blood monocytes from either patients or controls. The decreased response of peripheral-blood monocytes from patients with RA was found to be mediated by inhibitory serum factors, because the addition of patient sera to monocytes from healthy controls suppressed TNF-alpha response in the co-culture assay. Preincubation of monocytes from healthy controls with RA serum was sufficient to suppress the subsequent TNF-alpha response in T cell co-cultures, indicating that inhibitory factors do indeed bind to monocyte surfaces, which might represent a regulatory counter-action of the immune system to the long-standing and consuming autoimmune process in RA. There are some indications that apolipoprotein A-1 might be part of this regulatory system.
Arthritis Res Ther 2005
PMID:The contact-mediated response of peripheral-blood monocytes to preactivated T cells is suppressed by serum factors in rheumatoid arthritis. 1627 71

There is increasing epidemiologic evidence implying a role for chronic infection in atherosclerosis and that microbial TLR agonists may contribute to this disease. Mycoplasma arthritidis is an agent of acute and chronic inflammatory disease in rodents, and has been used extensively as a model for defining the mechanisms involved in arthritis and other inflammatory diseases. We have purified a 28-kDa, apolipoprotein A-1 (apoA-1)-like TLR2-dependent macrophage-activating moiety from a culture of a virulent strain of M. arthritidis. ApoA-1 similarly isolated from uninoculated mycoplasma medium was without bioactivity. The activity of the mycoplasma-derived molecule was resistant to heat and to digestion with proteinase K, but was susceptible to alkaline hydrolysis and H(2)O(2) oxidation. Infrared profiles of normal apoA-1 and that derived from mycoplasma were distinct. Unlike the activity of other mycoplasmal TLR2 agonists such as macrophage-activating lipopeptide-2, activity of the M. arthritidis-derived 28-kDa component was dependent upon CD14, a coreceptor for LPS. Finally, we showed that bioactive lipopeptides prepared from M. arthritidis grown in serum-free medium and also from a 41-kDa known bioactive lipoprotein of M. arthritidis, avidly bound to purified apoA-1 that separated out by SDS-PAGE, induced TNF-alpha and IL-12p40 both in vitro and in vivo. ApoA-1 is a key functional component of the high-density lipoprotein cholesterol complex by scavenging and removing unwanted lipids. Our finding that this molecule can acquire macrophage-activating properties from microbial TLR2-dependent agonists suggests a novel mechanism whereby some microbial agents might reverse the protective role of apoA-1, thus contributing to the genesis of atherosclerosis.
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PMID:A microbial TLR2 agonist imparts macrophage-activating ability to apolipoprotein A-1. 1698 24

Chlamydophila (Chlamydia) pneumoniae is an intracellular respiratory pathogen known to cause community-acquired pneumonia. Infection with this organism has been associated with atherosclerosis, inflammatory arthritis, and other chronic diseases, many of which also have been associated with possession of the epsilon4 allele at the APOE locus on (human) chromosome 19. An earlier study from this laboratory suggested that some relationship exists between apolipoprotein E4 (apoE4), the product of the epsilon4 allele, and the pathobiology of C. pneumoniae. A standard attachment assay and real time PCR targeting a sequence on the C. pneumoniae chromosome were used to monitor host cell binding of elementary bodies (EB) of that organism. Our data indicate that 3-fold more EB of strain AR-39 attach to an epsilon3 homozygous human cell line transfected with a plasmid expressing the epsilon4 coding sequence than to the same cell line harboring empty vector, vector containing an irrelevant insert sequence, or vector containing the DNA sequence encoding apoE3. The quantitative real time data were confirmed by immunolabeling of chlamydial inclusions in parallel attachment and infection assays. Experiments using Chlamydophila trachomatis EB showed no enhancement of attachment in the presence of the epsilon4 allele in any assays. These observations indicate that apoE4 enhances attachment of C. pneumoniae EB, but not those of C. trachomatis, to target host cells.
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PMID:Apolipoprotein E4 enhances attachment of Chlamydophila (Chlamydia) pneumoniae elementary bodies to host cells. 1799 73

To evaluate the therapeutic potential of an apolipoprotein A-1 (apoA-1) mimetic peptide, D-4F, in combination with pravastatin in collagen-induced arthritis (CIA), syngeneic Louvain rats were immunized with type II collagen and randomized to vehicle control, D-4F monotherapy, pravastatin monotherapy, or D-4F + pravastatin combination therapy. Clinical arthritis activity was evaluated and radiographs, type II collagen antibody titers, cytokine/chemokine levels, and HDL function analysis were obtained. There was significant reduction in clinical severity scores in the high and medium dose D-4F + pravastatin groups compared to controls (p< or =0.0001). Reduction in erosive disease occurred in the medium/high dose combination groups compared to non-combination groups (p< or =0.01). Favorable changes in cytokines/chemokines were noted with treatment, and response to combination D-4F/pravastatin therapy was associated with improvement in HDL's anti-inflammatory properties. Combination D-4F/pravastatin significantly reduced clinical disease activity in CIA, and may have dual therapeutic potential in other autoimmune diseases with increased cardiovascular morbidity and mortality.
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PMID:Treatment with an apolipoprotein A-1 mimetic peptide in combination with pravastatin inhibits collagen-induced arthritis. 1833 76

In a study published recently in Arthritis Research & Therapy, Woo and colleagues investigated the effects of pravastatin in combination with an apolipoprotein-AI (Apo-AI) mimetic peptide in a mouse model of lupus-accelerated atherosclerosis. Combination treatment resulted in a significant decrease in systemic inflammation but increased aortic root lesion size. However, this treatment changed the phenotype of the lesion to a more stable plaque. Because plaque stability is also important for protection against the deadly manifestations of atherosclerosis, combination therapies using Apo-AI mimetics and statin might offer a good additional therapy to treat autoimmunity and cardiovascular disease in patients with lupus.
Arthritis Res Ther 2010
PMID:Sizing up stability: combination therapy with Apo-AI peptide mimetics and statins in systemic lupus erythematosus-mediated atherosclerosis. 2048 80

Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers". Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE")-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14-22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms (63%), suggesting a spectrum for JRA to later FMS presentations. Likewise, persons reporting a history of attention deficit disorder (ADD) had an increased proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%). Toxic environmental exposures are common (23%) and associated with diagnoses of PSP, PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic exposure and PSP, PPA and FTD-PD. Our findings support the ICE behavioral phenotype for A1AT polymorphism carriers and the reported association with anxiety and bipolar spectrum disorders. We now extend that phenotype to apparent vulnerability to inflammatory muscle disease in a spectrum from JRA to fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific late onset neurological syndromes (FTD-PD and PPA). High and low risk FMS subsets can be defined using A1AT, MTHFR and APOE genotyping. Clinical diagnoses associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer Disease subtypes. These results support an extended phenotype for A1AT mutation carriers beyond liver and lung vulnerability to selective advantages: ICE phenotype and disadvantages: fibromyalgia, affective disorders, and selected late onset neurological syndromes.
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PMID:Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are not always silent. 2241 31