• Joseph V Bonventre.
• Renal Division, Brigham and Women's Hospital and Department of Medicine, Harvard Stem Cell Institute, Harvard Medical School and Harvard-Massachusetts Institute of Technology, Boston, MA 02115, USA. joseph_bonventre@hms.harvard.edu
• Contrib Nephrol. 2007 Jan 1; 156: 39-46.

AbstractThe pathogenesis of acute kidney injury (AKI) is complex and varies to some extent based on the particular cause. Inflammation contributes to this pathophysiology in a variety of contexts. Inflammation can result in reduction in local blood flow to the outer medulla with adverse consequences on tubule function and viability. Both the innate and adaptive immune responses are important contributors. With ischemia/reperfusion endothelial cells upregulate a number of adhesion molecules which have counterreceptors on leukocytes. A number of vasoactive mediators that are released with injury, such as nitric oxide, may also affect leukocyte- endothelial interactions. Tubule epithelial cells generate proinflammatory and chemotactic cytokines. We and others have found that injection of mesenchymal stem (stromal) cells is protective against renal injury as assessed by serum creatinine measured 24 h after ischemia. The mechanism of such protection may be through intrarenal paracrine effects to decrease inflammation or by systemic immune modulation. Resolvins (Rv) and protectins (PD) have been identified as two newly identified families of naturally occurring n-3 fatty acid docosahexaenoic acid metabolites. In collaboration with Serhan et al. we recently reported that, in response to bilateral ischemia/reperfusion injury, mouse kidneys produce D series resolvins (RvDs) and PD1 [J Immunol 2006;177:5902-5911]. Administration of RvDs or PD1 to mice prior to, or subsequent to, ischemia resulted in a reduction in functional and morphological kidney injury. Understanding how these anti-inflammatory processes are regulated may provide insight into how we might intervene to facilitate and enhance them so that we might prevent or mitigate the devastating consequences of AKI.

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