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NF-κB and MAPK expression in adjuvant arthritis

Author: ShenZuo
Tutor: FangXiuBin
School: China Medical University
Course: Human Anatomy and Embryology
Keywords: Rheumatoid arthritis Adjuvant arthritis Nuclear factor kappaB P65 Mitotic source activated protein kinase p38
CLC: R593.22
Type: PhD thesis
Year: 2003
Downloads: 268
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Abstract


Introduction Rheumatoid arthritis (RA) is an autoimmune disease, the pathological changes of the synovial tissue hyperplasia, inflammatory cell infiltration, and bone and cartilage irreversibility progressive destruction. Its pathogenesis is not entirely clear. Clinical rheumatoid lung involvement is more common. The rheumatoid lung injury is due to the increase in external stimulation factors secreted by inflammatory cells, alveolar macrophages and lung tissue inflammatory cytokine production, the alveolar deformation alveolar basement membrane and vascular wall damage caused alveolitis pulmonary vascular inflammatory changes, to stimulate lung fibrous tissue replication, synthesis, resulting in a large number of collagen accumulation, and ultimately the formation of fibrosis. Studies have shown that many of the inflammatory cytokines in RA synovial levels, such as TNF-α, IL-1, IL-6, IL-8, ICAM-1, the MMP, etc.. Many cytokines and inflammatory mediators involved in the pathogenesis of rheumatoid lung. A result of these proinflammatory cytokines increased expression of how the mechanism and its damaging effects on the joints, has attracted the interest of more and more scholars. One signaling system - sphingomyelin pathway has become a hot topic. When the external stimuli factors such as TNF-α, IL-1β, the growth factor in combination with a receptor on the cell membrane, activation of neutral sphingomyelinase (SMase), enzyme sphingomyelin (SM) can be hydrolyzed to ceramide (CM ). CM as a second messenger, some activated MAPK partial activation of NF-kappa B. Nuclear transcription factor κB (nuclear factor-kappa B, NF-κB) is initially from a B cell nuclear extract by sen et al discovered a with the enhancement of the immunoglobulin κ light chain gene sub-κB sequence (GGGACTTTCC) specific binding of nucleoprotein. Can promote the expression of the light chain gene. Later discovered that it is widely present in many cell types, can control the expression of many genes. These genes may encode cytokines, chemotactic factors, growth factors, cell adhesion factors and some of the acute phase response proteins, etc.. The mitogen sources cell proliferation and passed the key stress signaling protein kinase activated protein kinase (mitogen-activated protein kinase, MAPK), to many cytokines signaling plays an important intermediary role. The study showed that its phosphorylation can activate many transcription factors, such as c-fos and c-jun and c-myc, leading to increase in some inflammatory cytokines produced. NF-κB and MAPK are involved in the expression of many immune and inflammatory response genes, its role in the pathogenesis of RA has been a cause of concern. Worth exploring whether to participate in the pathological process of RA synovial and lung tissue lesions. Experimental method: tricky cases of RA in patients with previously untreated and clever healthy controls were peripheral blood lymphocytes were separated smear by immunohistochemistry to observe the expression of NF-KB, lymphocytes were counted NF-KB nuclear stained positive rate, a G, IgMRF, C3, C4 and ESR of whether the correlation analysis with r. The second experiment: Wistar rats right after a full bowel intradermal sterile injection of CFA (with BCG 7 .5 m year-old resistance) 0.1 girl animal models to the preparation of rheumatoid arthritis (RA) adjuvant arthritis (AA). Studies using in situ hybridization histochemistry the AA rat synovial MAPKmRNA amount of change, synovial membrane of NF-KB expression changes in AA rats using immunohistochemical staining. The application of microscopic image analysis system for quantitative analysis of its expression. Experiment: westeo blot method to study the activation of NF-KB protein levels in the AA rat lung tissue, further research the AA rat lung tissue NF KBmRNA level of its distribution, by in situ hybridization with microscopic image analysis system its Expression quantitatively analyzed. Experimental results 1.1 recognized in patients with peripheral blood lymphocytes of NF-KB nuclear staining positive rate was significantly higher than the control group (p lt; 0.01), and r G, IgMRF into positive correlation, the correlation coefficients were 0.577 and 0.656 (p lt ; 0.05, p lt; 0.01), and C3 into negatively correlated with a correlation coefficient of 0.736 (p lt; 0.0 a), no correlation with C4 and ESR. Microscope visible thickening of the the AA rats synovial lining cell layer, a large number of lymphocytic infiltration. Also seen a lot of lymphocytic infiltration and destruction of bone and cartilage, also visible formation of vascular Weng, comply with rheumatoid arthritis synovial pathological changes in the articular cartilage and bone. AA rat lung tissue seen in alveolar epithelial necrosis, alveolar deformation, alveolar capillary basement membrane damage. Interstitial lymphocytes, plasma cells and macrophage infiltration. The alveolar capillary base a lot of infiltration of lymphocytes, in line with the pathological changes of rheumatoid lung. AA rats synovial NF-KB degree of positive staining was significantly stronger than the normal control group (p lt; 0.01). The distribution of positive cells in the synovial lining cells, macrophages, into the fiber cells and lymphocytes. Cytoplasm and nuclei were stained, but the deep nuclei staining, mostly lumpy distribution cytoplasmic staining shallow. Weak positive staining is visible in normal rat synovial lining cells and fibroblasts. The the AA rats synovial, P38mRNA staining positive was significantly stronger than the normal control group (p lt; 0.01). Positive cells were mainly distributed in the synovial lower. Including macrophages, fibroblasts and lymphocytes. Full of brown particles in the cytoplasm was granular or lumpy distribution, and occasionally a small amount of staining nuclei. Synovial lining layer of cells staining reaction was negative. Also visible articular bone and cartilage destruction seen in P38mRNA reaction positive lymphocyte infiltration. Weakly positive staining in the normal rat synovial into fibroblasts and macrophages visible negative staining in the synovial lining cells. The correlation analysis found P38mRNA of NF-KB was significantly positively correlated (r 0.725, p lt; 0 .01). 4.AA rat lung tissue activated P65 protein (nuclear protein) levels were significantly higher (p lt; 0.01). And the AA rat lung tissue p65mRNA expression was significantly higher than the normal control group (p lt; 0.01). P65mRNA mainly expressed in the lungs of macrophages, plasma cells, and the dip of human lung interstitial lymphocytes. Visible full of yellow-brown granules in the cytoplasm, was granular or mass distribution. The conclusion 1.RA peripheral blood of patients to lymphocyte activation of NF-KB expression may be involved in the pathogenesis of RA, and was positively correlated with the severity of the disease. 2.AA rat synovial cells (synovial lining cells, macrophages, fibroblasts and infiltrating lymphocytes), increased expression of NF-KB protein may be involved in the pathological process of the synovium. 3.MAPKmRNA in AA in synovial

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Rheumatoid arthritis
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