Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.
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PMID:Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. 150 84

The presence of neutrophils in the synovial joint of patients with rheumatoid arthritis (RA) is thought to be due to the activity of chemotactic factors released by activated cells in the joint. We have shown in this report, for the first time, the abundance of one such factor, interleukin 8 (IL 8), in the synovial fluid of patients both with RA and other non-RA joint diseases, and the spontaneous production of IL 8 mRNA by RA synovial cells in culture. There was no correlation between the levels of chemotactic activity and IL 8 protein, suggesting that other factors with similar neutrophil chemotactic activity are also present in the synovial fluid exudate. In support of this concept neither the level of chemotactic activity nor IL 8 protein levels correlated with neutrophil or leukocyte infiltration, indicating that the mechanism of migration into the inflammatory environment of the joint is complex. Such migration is likely to be due to a number of chemotactic signals in addition to IL 8, which may either synergize with, or inhibit, the action of IL 8.
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PMID:Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. 220 7

The pX gene of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of the viral gene and the host genes which are important for cell proliferation in vitro. It has been reported that various diseases occur in transgenic mice harboring either tax, pX, or env-pX gene, such as mesenchymal tumor, neurofibroma, thymic atrophy, muscle degeneration, exocrinopathy and arthropathy. We previously demonstrated that rat but not mouse CD4 positive T cells could be easily infected and immortalized by HTLV-I and infectious transmission of HTLV-I induced HAM/TSP-like myelopathy in WKAH rats after long incubation periods of 16 months. These observations prompted us to produce a series of transgenic rats that expressed the pX gene products under the control of mouse H-2Kd promotor in order to evaluate further the biological and pathological function of the pX gene in vivo. In various tissues of pX transgenic rats (pX rats), pX mRNA was constitutively expressed irrespective of age. PX rats developed mammary tumors with massive infiltration by neutrophils as early as 9 months of age. Pathological and immunohistochemical examination revealed that the tumors were undifferentiated carcinomas of the mammary gland origin. They were transplantable into pX rats, but not into normal syngenic rats. High levels of mRNA expression of not only the pX transgene but also the host genes such as Gro (melanoma growth-stimulatory activity/KC), MIP-2 (macrophage inflammatory protein-2) and IL-1 alpha were demonstrated in the tumor tissues. Gro and MIP-2 which were known as IL-8 families were likely to be produced by tumor cells and appeared to be responsible for neutrophil infiltration in the tumor tissues. Lastly, pX rats described here appear to be suitable animal models for elucidating mechanisms involved in the tumorigenesis and the transactivation of the cellular genes by HTLV-I, especially by the pX gene products in vivo.
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PMID:[Pathological and molecular analyses of mammary tumors induced in HTLV-I pX transgenic rats]. 792 76

Rheumatoid arthritis and related inflammatory joint diseases are characterized by massive infiltration of polymorphonuclear cells (PMN) into inflamed joints. Interleukin-8 (IL-8) has recently been identified as a leukocyte chemotactic and activating factor produced by activated tissue cells as well as monocytes/macrophages. Examination was made of the involvement of IL-8 in acute arthritis induced by injecting lipopolysaccharide (LPS) or interleukin-1 alpha (IL-1 alpha) into the joints of rabbits. The neutralizing antibody to rabbit IL-8 blocked almost completely the infiltration of PMN into the joints and provided protection from damage to tissue in the early phase of inflammation induced by LPS or IL-1 alpha. Mononuclear cell infiltration observed later was not inhibited by this antibody. This is the first paper to clearly demonstrate that IL-8 is an essential and major mediator determining whether PMN infiltration will occur in the early phase of experimental acute arthritis.
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PMID:Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute experimental arthritis induced by lipopolysaccharide and interleukin-1. 806 Nov 12

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease continues to be of intense clinical and basic science interest. Follow-up of studies of hereditary CPPD crystal deposition indicate differences from the common sporadic disease. The results of a prospective study of CPPD crystal deposition arthropathy confirm that clinical symptoms appear to be independent of radiologic progression. Novel clinical presentations include association with pregnancy and simulation of meningitis. CPPD crystal deposition pathology in synovium ultrastructurally resembles that in cartilage. Factors such as the presence of ATP can induce experimental calcifications in tissue culture that resemble CPPD crystal deposition. Interleukin-8 and tyrosine phosphorylation of neutrophil protons can mediate CPPD crystal deposition-associated inflammation. The control of crystal function and dissolution recently has been the subject of many general reviews. The theory outlined in these papers is important for understanding CPPD crystal deposition and basic phosphate crystal formation and dissolution.
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PMID:Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. 806 17

High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1 beta, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL-beta detectable levels (> or = 20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA. IL-6 (mean +/- SD) (1610.37 +/- 1781.65 pg/ml) was higher in RA than in PA (672.47 +/- 867.40 pg/ml, p = 0.043) and OA (89.45 +/- 120.52 pg/ml, p = 0.0001). IL-8 (1042.72 +/- 698.64 pg/ml) was higher in RA than in PA (660.36 +/- 625.11 pg/ml, p = 0.03) and OA (89.9 +/- 45.88 pg/ml, p = 0.0001). A correlation between IL-1 beta, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration. Our findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.
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PMID:Interrelationships between interleukin (IL)-1, IL-6 and IL-8 in synovial fluid of various arthropathies. 807 29

Interleukin-1 receptor antagonist (IL-1ra) has the potential to counteract at least part of the biological effects of interleukin-1. The outcome of an inflammatory reaction may therefore be determined by the balance between IL-1 and IL-1ra, rather than by IL-1 alone. We have developed an immunoassay to address this issue as well as to assess the effects of anti-inflammatory agents on the expression of IL-1 and IL-1ra in vitro or in body fluids. Recombinant human IL-1ra was expressed in an E. coli system, purified to homogeneity, and used to derive monoclonal antibodies in mice as well as polyclonal antibodies in rabbits. A sandwich ELISA was constructed with F(ab')2 fragments of a high affinity monoclonal antibody and the rabbit serum as a source of secondary antibody. The assay required no sample treatment to avoid interference by rheumatoid factor. The measuring range was 0.020-2 ng/ml. By labelling a second monoclonal antibody with an acridinium ester, a chemiluminescence assay with a wider measuring range (0.050-15 ng/ml) was generated. In accord with published data, we found that IL-1ra was secreted by human monocytes stimulated with LPS, Zymosan, IL-1 alpha, or human IgG. After an induction phase of ca. 4 hours and depending on the stimulus, IL-1ra accumulated linearly for periods up to 96 h. IL-1ra levels in synovial fluids of 19 patients suffering from various inflammatory joint diseases were compared with the cytokine levels of IL-1 beta, IL-6, IL-8, and TNF-alpha. Highest positive correlations were found with IL-8 and IL-1 beta. In normal blood donors IL-1ra serum levels were 150-800 pg/ml (Median: 387 pg/ml). Owing to its sensitivity and large measuring range the newly developed assays appear to be suitable for measuring IL-1ra in cell cultures as well as in biological fluids.
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PMID:Monoclonal antibody based enzyme-linked and chemiluminescent assays for the human interleukin-1 receptor antagonist. Application to measure hIL-1ra levels in monocyte cultures and synovial fluids. 815 85

Macrophages infiltrated into synovium play an important role in joint destruction in inflammatory joint diseases. In this study we focused on the production of monocyte chemoattractant protein-1 (MCP-1), a recently identified monocyte chemotactic protein, by inflammatory synovium. Synovial fluid (SF) from rheumatoid arthritis (RA), osteoarthritis, gout, and traumatic arthritis contained MCP-1. MCP-1 was produced in the synovium of patients with RA and other inflammatory joint disease in in vitro culture systems; differences in the amounts produced were not significant. Synovial MCP-1 production in RA was further investigated. Levels of MCP-1 were significantly correlated with levels of IL-1 beta, IL-6, and IL-8 in the culture supernatants of synovia from RA. Using immunohistochemical techniques, MCP-1 was detected in the lining and sublining cells and in the vascular endothelial cells of rheumatoid synovia. Rheumatoid synovia with active inflammation were stained more intensely by anti-MCP-1 antibody than were those with weak or inactive inflammation. IL-1 beta and TNF-alpha stimulated the expression of MCP-1 mRNA and de novo MCP-1 synthesis by cultured synovial cells. These results suggest the production of MCP-1 by synovium of various inflammatory joint diseases. In rheumatoid synovium, a cytokine network involving MCP-1 and other proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) contributes to the immunopathogenesis of RA.
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PMID:Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. 840 45

Cytokines are potent regulators of the chondrocyte functions. Some of them are produced by chondrocytes and interact to regulate cartilage metabolism. In this study, we investigated the production of interleukin-1 beta (IL-1 beta), IL-6, IL-8 and leukemia inhibitory factor (LIF) by human chondrocytes and examined the modulation of their secretion by exogenous cytokines. Human articular chondrocytes were isolated from their extracellular matrix by a triple successive enzymatic digestion of the cartilage. Subsequently, chondrocytes were stimulated by increased amounts of human recombinant cytokines [IL-1 beta, tumour necrosis factor alpha (TNF alpha), IL-8, LIF, IL-6]. IL-1 beta, IL-6, IL-8 and LIF were assayed into culture media and inside cell extracts by specific enzyme amplified sensitivity immunoassays (EASIAs). Under these experimental conditions, we have identified various interactions between cytokines. IL-beta and TNF alpha highly stimulated IL-6, LIF and IL-8 productions. IL-6 decreased IL-8 synthesis and increased LIF production. IL-8 slightly enhanced IL-6 production. Finally, LIF stimulated IL-1 beta, IL-6 and IL-8 productions. Using neutralizing antibodies against IL-1, we demonstrated that the effects of LIF were secondary to the stimulation by LIF of IL-1 beta production by the chondrocytes. In conclusion, chondrocytes secrete a variety of immunocompetent cytokines including IL-1 beta, IL-6, IL-8 and LIF that can interact to regulate chondrocytes metabolism. These results also define new biological activities of LIF and IL-6, and raise questions concerning their role in the pathogenesis of joint diseases.
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PMID:Effects of exogenous IL-1 beta, TNF alpha, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes. 889 17

Synovial fibroblasts from patients with osteoarthritis in culture produced parathyroid hormone-related peptide (PTHrP) on treatment with phorbol ester (TPA) in a dose- and time-dependent manner. The levels of PTHrP immunoreactivity in the conditioned medium of synovial fibroblast cultures were measured using specific PTHrP antibody. The maximum production was obtained at a concentration of 10(-8) M and 24 h after TPA treatment. But sensitivity to TPA of synovial fibroblasts differed among four patients from slight to marked. PTHrP production was also induced with inflammatory cytokines, such as 1 ng/ml of IL-1alpha, IL-1beta, IL-6 and TNF-alpha, and 10(-6) M prostaglandin E2, after 24 h treatment. The expression of PTHrP was confirmed by reverse-transcriptase polymerase chain reaction. Since the synovial fibroblasts isolated from osteoarthritic patients produce high levels of IL-6 and IL-8, typical cytokines produced in synovial fibroblasts, production of PTHrP may provide new insight into the pathophysiology of joint disorder.
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PMID:Production of parathyroid hormone-related peptide by synovial fibroblasts in human osteoarthritis. 974 21


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