The Role Of IκBα In Regulation Mechanism Of Viral Transactivation Of Transcription In Patients With Steroid Responsive Simple Nephrotic Syndrome

Objective:The etiological factors and pathogenesis of minimal change nephrotic syndrome (MCNS) are still unclear up to now. Our previous studies in airway epithelial cells and peripheral blood mononuclear cells and other clinical observation demonstrated that respiratory tract viruses infection may be the most important factor of all etiological factors. Respiratory tract viruses induced NF- K B activation may trigger MCNS. However ,there isn't study of IicBa inhibitory effect on NF- K. B. Studies presented here attempt to insight into the regulation mechanism of NF- B activation by IicBa in peripheral blood mononuclear cells of the patients with steroid responsive simple nephrotic syndrome .Methods:NF- K B activation in PBMC was observed by electro-mobility shift assays(EMSA).Western blot was used to determine IicBa protein levels. Quantitative analysis of IicBa gene transcription was performed with TaqMan RT-PCR. Furthermore ,we study the relationshipbetween the NF- K B activation and IicBa protein levels.Results:1 .Compared with remission group of SRSNS > primary nephritic nephrotic syndrome group -. other secondary renal glomerular disease and healthy control group,NF- K B activation in PBMC of the patients with SRSNS at active stage was much higher statistically(P<0.05). In addition,Respiratory syncytial viruses were the most frequently detected in SRSNS. There was a positive correlation tread between NF- K B activation and the gene expression of respiratory tract viruses in PBMC of the patients with SRSNS at active stage. 2. IicBa mRNA levels in PBMC of the patients with SRSNS at active stage were much higher than that of normal control group(4691.68+1112.79 vs. 942.07+147.29,PO.001),but much lower than that of primary nephritic nephrotic syndrome group -. other secondary renal glomerular disease. Our results indicated that the increase in IxBa mRNA expression is likely due to increased gene transcription.3. IicBa protein levels in PBMC plasm of the patients with SRSNS at active stage were much lower ihan not only that of normal control but also that of primary nephritic nephrotic syndrome group -. other secondary renal glomerular disease(P<0.05).Our results support the hypotheses that IicBa proteolysis occurs independently of the protease pathway during respiratory tract viruses infection. 4.There was a linear negative correlation of elevated NF- SRSNS at remission stage(P<0.05).At the same time ,IicBa mRNA and IicBa protein levels in PBMC of the patients with SRSNS at relapse stage and remission stagewith GC therapy were higher than those in PBMC of the patients with SRSNS at incipient stage (P<0.05).Our results indicated that GC inhabits NF- K B activation due to enhanced IicBa gene transcription and IicBa protein synthesis partially.Conclusion:The viral transactivation of transcription plays an extremely role in triggering SRSNS by respiratory tract viruses. IicBa gene transcription elevated because of NF- K B. IicBa autoregulation loop;but IicBa protein levels can't restore to normal likely due to IicBa proteolysis via non-protease S26 pathway. Decendening Ixfia protein levels may associate with elevated NF- K B activation. Increasing IxBa protein levels may attribute to suppressing NF- K B activation and reducing SRSNS relapse.