Guidance Cue Netrin-1 and the Regulation of Inflammation in Acute and Chronic Kidney Disease

Figure 5

Pathways of inflammatory mediators and their regulation of netrin-1 during ischemia reperfusion injury of the kidney. Ischemic insults initiate inflammation in the kidney through activation of NFκB mediated COX-2 expression and prostaglandin E2/thromboxane production. These mediators, acting through an autocrine or paracrine mechanism, stimulate the production of cytokine and chemokines from monocyte (MΦ), neutrophils, and dendritic cells (DC). T cells may be activated through DC or direct activation by soluble mediators released from other cells or receptor mediated mechanism. Activation and release of soluble mediators from these white blood cells cause vascular leakage, edema, hypoxia, and tubular epithelial cell damage which will be manifested as kidney dysfunction. Netrin-1 reduces the severity of these events by acting at multiple levels through downregulation of COX-2 expression and suppression of inflammatory mediators production.