| Immune tolerance is a state of systemic unresponsiveness specific for a particular foreign antigen to protect body from autoimmunological disease induced by this antigen. Presentation of these antigens along mucosal surfaces by oral feeding or intragastric intubation is an effective and recognized method of inducing peripheral hyporesponsiveness, and this phenomenon is often referred to as oral tolerance. Recently, it is believed that a defect of auto-immunological tolerance presents in the patients with primary glomerulonephritis, and the interaction among autoimmunological cells, imflammation cells and intrinsic cells in kidney leads to the auto-immunological renal lesion. Nowadays, the major therapy with immunosuppressive agents for glomerular disease with long term may have many side effects, and decreased dose or withdrawal of these drugs may result in the relapse of disease. Consequently, how to reduce or prevent the relapse of nephritis is needed to be solved for clinic physicians. Nuclear-κB (NF-κB)is an important transcription factor to introduce signal transduction in cells. Activation of NF-ΚB can regular immunity, inflammatory reaction and cells growth byupregular the transcription of genes. In glomerular diseases, many factors can accelerate the activation of NF-κB in intrinsic cells or inflammatory cells in kidney which can secrete inflammatory medium, so NF-κB may play an important role in inducing or deteriorating glomerular diseases. Nevertheless, the change of activity of NF-κB in oral tolerance is not still documented. Objective: ①To study the prevention of active Heymann nephritis (AHN) by oral tolerance and the change and significance of activation of NF-κB p65 during this process.②To study the effect of lymphocytes from orally tolerized rats on the activation of NF-κB p65 in mesangial cells.Methods: Female Wistar rate weighing about 80g were divided into three groups: oral tolerance group, AHN model group and control group. Then, we observed as follow:①the changes of immunological function,renal pathology, urine protein and serum albumin ,and the activation of NF-κB p65 in splenic lymphonodi and renal,②the effect of lymphocytic medium prepared from the cultured splenogenous lymphocytes from rats in oral tolerance group on activation of NF-ΚB p65 in mesangial cells.Results: ①Compared with the control group and nephritis group, the splenogenous lymphocytes proliferation assay and delayed-type hypersensitivity response were suppressed significantly in oraltolerance group, ②Compared with control group, the activity of NF-κB p65 of PP lymph nodes and splenic lymph tissue were obviously expanded in rats of oral tolerance group and AHN model group; and the activity of NF-κB p65 in PP lymph nodes was enhanced more in rats of oral tolerance group than in that of AHN model group, but such activity declined in splenic lymphonodi. The expression of TGF-β1 in splenic lymphonodi was elevated more in oral tolerance group rats than in nephritis group rats.③The glomerular base membrane (GBM) was thicker, and the lesion severity score of kidney interstitial proliferated more in AHN model group rats than control group rats,with IgG deposition in GBM by immunoflurescence, an elevated urine protein and lower levels of serum albumin. However, the renal pathological lesion in orally tolerized rats alleviated much.④A significant increase in the number of NF-κB p65 positive introglobular cells and the positive rate of renal tubules was observed in AHN model group and oral tolerance group, but there was a decline in rats of oral tolerance group when compared with AHN model group.⑤There was a positive line-correlation and regression relation between the activation of NF-κB p65 and the pathological lesion in kidney tissue of rats in AHN model group and oral immune tolerance group. ⑥The activation of NF-κB p65 in splenic lymphocytes were also related with that in kidney tissue and therenal pathological lesion.⑦Compared with the normal MCs cultu... |
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