| PrefaceRheumatoid arthritis (RA) is an autoimmune diseases that leads to chronic inflammation in the joints, functional disability and increased mortality. The pathological changes of RA are mainly about synovium proliferation, inflammatory cells infiltration and the irreversible damage of bone and cartilages in joints. Many studies showed that the expression of pro - inflammatory cytokines increased in RA synovium, such as TNF-a,IL-1,IL-6, IL-8 and ICAM -1 etc. RA pulmonary involvement is mainly due to the increase secretion of proinflammatory cytokines by alveolar phagocytes under the external stimulations. At the same time, the inflammatory cells that infiltration into the lung tissue also can secret some inflammatory mediators, which damage the basilar membranes and the walls of pulmonary arterioles, result in alveolitis and pulmonary vasculitis.Whats the mechanism for the increased expression of pro - inflamatory cytokines and for their actions on tissues? One kind of signal transduction pathway- sphingomyelinase pathway became the key point to study. The external stimulated factors combined with the receptors on plasma membrane , which activated neutral sphingomyelinase(SMase) . By the action of SMase , plasma membrane sphingomyeline(SM) was hydrolyzed into ceramide(CM) . CM serve as a second messenger , stimulating a Ser/Thr ceramide-activated protein kinase to transduct the cytokine signal , in part through transcription factors such as nuclear factor B(NF-B) and mitogen activated protein kinase (MAPK).NF-B is a transcription factor that is recognized to play a pivotal role in the regulation of inflammation. It was initially discovered as a regulator of light- chain gene expression in B cells, but subsequent studies revealed that it is present in many different cell types. NF - KB can activate transcription of many genes involved in immune and inflammatory responses, including TNF, IL-1, IL-6, IL-8,GM-CSF ,ICAM-1 etc.MAPK is a kind of key protein kinases in cell proliferation and stress signal conduction. It is an important intermediateors in cytokines signal transduction pathways. The best characterized subfamilies of the MAPK superfamily are the extracellularly responsive kinases ( ERKs) , the c - jun N - terminal kinases (JNKs) and the p38MAPKs. Several substrates of MAPK have been identified that are distributed within different subcellular compartments, such as c - jun, c - myc, c - fos, ATF - 2, NF - IL6 etc, and it is likely that many additional substrates will be described. In this study, we observed the expression of NF -KB and MAPK ( p38 ) mRNA in RA patients and adjuvant arthritis ( AA ) , to study the pathogenesis of RA.Methods1. Peripheral lymphocytes from 15 RA patients and 15 healthy controls were separated and smeared, the expression of NF - KB in these cells was studied by immunohistochemistry and analyzed quantitatively by counting the positive percents of lymphocytes nuclear staining. Furthermore, we investigated the correlations between NF-B and r-G, IgMRF, C3, C4 , ESR.2. Subcutaneous injection of CFA( contain BCG 7. 5mg/ml)0.1ml into right-posterior foot metatarsus of male wistar rats to build the animal models of RA - AA. To detect the expression of p38mRNA by in situ hybridization histo-chemistry and of NF-B by immunohistochemistry in synovium of AA and normal rats. The intensity of expression was analyzed by microimage analysis system.3. To detect the level of active NF-B protein by western blot and of NF -BmRNA by in situ hybridization histochemistry in the lung tissues of AA and normal rats. The intensity of expression was analyzed by micro - image analysis system.Results1. The nuclear staining positive percentage of peripheral lymphocytes in RA patients was much higher than those of the healthy controls( p <0.01). Furthermore, there were positive correlations between NF -B and r - G(r =0. 577 ,p< 0.05 ) , IgMRF( r=0.656,p<0.01) , with negative correlation between NF -B and C3 ( r = - 0. 736, p < 0. 01) , no obvious cor...
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