Role of CXC Chemokine Receptor 3 Pathway in Renal Ischemic Injury
Open Access
- 1 March 2006
- journal article
- research article
- Published by Wolters Kluwer Health in Journal of the American Society of Nephrology
- Vol. 17 (3), 716-723
- https://doi.org/10.1681/asn.2005090954
Abstract
Chemokines play a major role in the recruitment of leukocytes in inflammation and in the regulation of T helper 1 (Th1)/Th2 immune responses. These mechanisms have been recognized to be important in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The interaction of the CXC chemokine receptor 3 (CXCR3) receptor with its ligands is a key pathogenic pathway in promoting inflammation and in enhancing Th1 immune responses. After the induction of ischemia in the mouse model of renal ischemia, an increase in intrarenal expression of CXCR3 and its ligands was observed. Compared with the wild-type (WT) mice, CXCR3-deficient mice (CXCR3−/−) had significantly lower serum creatinine levels, better survival rate, and significantly less acute tubular necrosis and cellular infiltrates. In the kidney, intracellular staining of infiltrating cells that were recovered from kidneys revealed a lower percentage of CD4+IFN-γ+ cells in the CXCR3−/− mice compared with the WT mice. Furthermore, adoptive transfer of WT CD3+ cells into CXCR3−/− mice before induction of I/R injury abrogated the protection of CXCR3−/− mice from I/R injury. It is concluded that CXCR3 plays an important role in orchestrating the recruitment of Th1 cells to the ischemic kidney and in mediating I/R injury and therefore may serve as a novel target for the therapy of I/R injury.Keywords
This publication has 45 references indexed in Scilit:
- Delayed graft function in renal transplantationCurrent Opinion in Critical Care, 2004
- Intrarenal Administration of Molsidomine, a Molecule Releasing Nitric Oxide, Reduces Renal Ischemia-Reperfusion Injury in RatsAmerican Journal of Transplantation, 2004
- Ischemic acute renal failure: An inflammatory disease?Kidney International, 2004
- Long-term effects of acute ischemia and reperfusion injuryKidney International, 2004
- Inflammatory cells in ischemic acute renal failureKidney International, 2004
- Prevention of apoptotic and necrotic cell death, caspase‐3 activation, and renal dysfunction by melatonin after ischemia/reperfusionThe FASEB Journal, 2003
- Protective effect of T cell depletion in murine renal ischemia-reperfusion injury.Transplantation, 2002
- Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemiaKidney International, 2001
- Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1Nature, 2000
- An emerging paradigm shift on the role of leukocyte adhesion molecules.JCI Insight, 1997