The role of innate immunity in chronic kidney disease stablished after recovery ne...
| Grant number: | 14/17031-9 |
| Support type: | Scholarships in Brazil - Scientific Initiation |
| Effective date (Start): | January 01, 2015 |
| Effective date (End): | December 31, 2015 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Roberto Zatz |
| Grantee: | Laís de Araujo Serra Braga |
| Home Institution: | Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury, AP.TEM |
Abstract Chronic Kidney Disease (CKD) is the result of multiple factors, including inflammatory events that lead to fibrosis of the renal parenchyma. However, its unclear how this inflammation is triggered in the absence of pathogens and other foreign substances to the body. Basing ourselves in accumulated knowledge, it is believed that the inflammatory process resulting from persistent activation of one or more components of innate immunity, including the NF-kB systemActivation of innate immunity begins by binding of DAMPs and PAMPS to toll like receptors (TLRs). DAMPS are endogenous proteins released when the cell undergoes some kind of aggression (hypoxia, ischemia, etc.). PAMPs, in turn, are exogenous proteins usually linked to cell membrane of microbial agents. These two types of molecules bind to TLR receptors on the plasma and endosomal membrane of antigen-presenting cells (APCs), macrophages and even epithelial cells. The resulting activation of intracellular pathways culminates in the asfenble of inflamassomes on one side, and triggering of the cascadeon the other. In both cases, pro-inflammatory cytokines are released.In a previous study from this laboratory, L-NAME, a potent nitric oxide inhibitor that causes glomerular hypertension and subsequent activation of NF-kB system, was administered along with a high salt diet, which intensified the effects of hypertension. This regimes was maintained for 3 weeks during wich marked proteinuria and glomerular and interstitial lesions developed. Withdrawal of this treatment resulted in regression of these previously reported harmful effects. However, six months later proteinuria had rises, together with the development of glomerulosclerosis and hypertension. A possible explain for this outcome is that activation of NF-kB system persisted after withdrawal of the initial insult.Based on that treatment with L-NAME and saline overload may cause activation of innate immunity and that this is an important factor in the development of CKD, the objective of the present work is investigate whether susppenssion of the NF-kB system has a predective effect on the late consequences of short-term NO inhibitors associated with salt overload. | |