Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overwhelming evidence suggests that ischemia-reperfusion injury of the kidney is an inflammatory disease mediated by innate and adoptive immune systems. The neuronal guidance molecule netrin-1 was shown to modulate inflammatory responses. Given that ischemic kidney is particularly prone to reperfusion-elicited inflammation, we sought to determine the function of netrin-1 and its receptor UNC5B in ischemia-reperfusion-induced inflammation. Renal ischemia-reperfusion caused a rapid decrease in serum netrin-1 levels. Administration of recombinant netrin-1 before or after renal ischemia-reperfusion reduced kidney injury, apoptosis, monocyte and neutrophil infiltration, and cytokine (IL-6, IL-1beta, and TNF-alpha) and chemokine (MCP-1, macrophage-derived cytokine, monokine-induced IFN-gamma, keratinocyte-derived chemokine, and chemokine with 6 cysteines) production. Analysis for different netrin-1 receptors on leukocytes showed very high expression of UNC5B but not UNC5C, UNC5D, neogenin, or deleted in colorectal cancer. Expression of UNC5A was low. Neutralization of UNC5B receptor reduced netrin-1-mediated protection against renal ischemia-reperfusion injury, and it increased monocyte and neutrophil infiltration, as well as serum and renal cytokine and chemokine production, with increased kidney injury and renal tubular cell apoptosis. Finally, investigation into netrin-1's effect on CD4 T cell stimulation showed suppression of Th1/Th2/Th17 cytokine (IL-2, IL-6, IL-10, IL-13, IL-17, IFN-gamma, IL-4, and TNF-alpha) production in vitro. Our studies demonstrate that netrin-1 acting through UNC5B receptor reduces renal ischemia-reperfusion injury and its associated renal inflammation.
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PMID:Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. 2069 23

The Th1/Th2 balance represents an important factor in the pathogenesis of renal ischemia-reperfusion injury (IRI). In addition, IRI causes a systemic inflammation that can affect other tissues, such as the lungs. To investigate the ability of renal IRI to modulate pulmonary function in a specific model of allergic inflammation, C57Bl/6 mice were immunized with ovalbumin/albumen on days 0 and 7 and challenged with an ovalbumin (OA) aerosol on days 14 and 21. After 24 h of the second antigen challenge, the animals were subjected to 45 minutes of ischemia. After 24 h of reperfusion, the bronchoalveolar lavage (BAL) fluid, blood and lung tissue were collected for analysis. Serum creatinine levels increased in both allergic and non-immunized animals subjected to IRI. However, BAL analysis showed a reduction in the total cells (46%) and neutrophils (58%) compared with control allergic animals not submitted to IRI. In addition, OA challenge induced the phosphorylation of ERK and Akt and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung homogenates. After renal IRI, the phosphorylation of ERK and expression of COX-2 and iNOS were markedly reduced; however, there was no difference in the phosphorylation of Akt between sham and ischemic OA-challenged animals. Mucus production was also reduced in allergic mice after renal IRI. IL-4, IL-5 and IL-13 were markedly down-regulated in immunized/challenged mice subjected to IRI. These results suggest that renal IRI can modulate lung allergic inflammation, probably by altering the Th1/Th2 balance and, at least in part, by changing cellular signal transduction factors.
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PMID:Modulation of lung allergic response by renal ischemia and reperfusion injury. 2250 59