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)

Renal ischemia-reperfusion injury (IRI) rapidly induces production of inflammatory mediators including, and in particular, tumor necrosis factor (TNF). Possible sources include resident parenchymal and bone marrow-derived cells as well as recruited leukocytes. Cell suspensions from kidneys subjected to IRI were examined by cell separation followed by in vitro culture and enzyme-linked immunosorbent assay (ELISA), immunoperoxidase and immunofluorescence microscopy, and multicolor flow cytometry to determine the contribution of dendritic cells (DCs) to early production of TNF and other inflammatory mediators. Secretion of TNF, interleukin (IL-6), monocyte chemoattractant protein-1 (MCP-1), and regulated on activation normal T cell expressed and secreted (RANTES) was increased in cell suspensions from IRI compared with control kidneys and was higher in DC-enriched preparations. Immunostaining identified TNF(+ve) cells that coexpressed the DC marker CD11c. Flow cytometry of bone marrow-derived (CD45(+ve)) cell populations at 24 h post-IRI demonstrated that F4/80(+ve)/CD11c(+ve) DCs remained proportionately stable and exhibit higher levels of DC maturation markers, whereas the proportion of F4/80(-ve) DCs, monocytes, neutrophils, and T cells increased. Intracellular staining for TNF confirmed that F4/80(+ve) DCs were the predominant TNF(+ve) cell and expressed higher levels than other TNF(+ve) cells. In vivo depletion of DCs from the kidney substantially attenuated TNF secretion by total and CD45(+ve) cells following IRI. The results uncover a role for resident F4/80(+ve) DCs as the predominant secretors of TNF within 24 h of IRI.
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PMID:Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury. 1738 9

Neutrophils and macrophages rapidly infiltrate the kidney after renal ischemia-reperfusion injury, however specific molecular recruitment mechanisms have not been fully delineated for these cell types. Here we provide genetic and pharmacologic evidence supporting a positive role for the chemokine receptor CCR1 in macrophage and neutrophil infiltration in a 7 day mouse model of renal ischemia-reperfusion injury. By day 7, injured kidneys from mice lacking CCR1 contained 35% fewer neutrophils and 45% fewer macrophages than injured kidneys from wild-type control mice. Pretreatment of wild-type mice with the specific CCR1 antagonist BX471 also suppressed neutrophil and macrophage infiltration in the model. Injured kidneys from mice lacking CCR1 also had reduced content of the CCR1 ligands CCL3 (MIP-1alpha) and CCL5 (RANTES) compared with injured kidneys from wild-type controls, suggesting a leukocyte source for these inflammatory chemokines and existence of a CCR1-dependent positive feedback loop for leukocyte infiltration in the model. Local leukocyte proliferation and apoptosis were detected after injury, but were not dependent on CCR1. Also, the extent of necrotic and fibrotic damage and decline in renal function in injured kidneys was similar in wild-type and CCR1-deficient mice. Thus, CCR1 appears to regulate trafficking of macrophages and neutrophils to kidney in a mouse model of renal ischemia-reperfusion injury, however this activity does not appear to affect tissue injury.
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PMID:Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury. 1905 Feb 87

Ischemia reperfusion injury (IRI) has long-term sequelae on kidney allograft function. Early initiation of rapamycin can retard surgical wound healing and recovery from IRI. In contrast, rapamycin may paradoxically retard long-term fibrotic effects of kidney IRI. We, therefore, hypothesized that delayed initiation of rapamycin after kidney ischemia, started after the initial week of wound healing, would decrease the long-term inflammation and fibrosis caused by IRI. C57BL/6 male mice were subjected to either 45 or 60 minutes of unilateral kidney ischemia or a sham operation. Mice were given rapamycin (subcutaneous, 1.5 mg/kg/d) or vehicle starting at 1 week after IRI surgery for 3 weeks. Urine albumin excretion, kidney histology, and kidney cytokine proteins were examined at 4 weeks after surgery. The 3-week treatment course of rapamycin significantly reduced body weight gain in all 3 groups and reduced postischemic kidney weight in both the 45- and 60-minute ischemia groups, but unexpectedly increased urine albumin excretion in all rapamycin-treated sham or IRI mice compared with vehicle-treated mice. Rapamycin treatment showed minimal effects on postischemic kidney fibrosis with variable effects on various cytokine/chemokine protein expressions, namely, decreasing interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and regulated on activation normal T cell expressed and secreted (RANTES) while increasing IL-4, keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP-1alpha), and IL-10 in the ischemic kidney. These data demonstrated that rapamycin reduced mouse body weight and ischemic kidney weight, while increasing urinary albumin excretion. Delayed initiation of rapamycin after IRI had a minimal effect on renal fibrosis and mixed effects on proinflammatory mediator production. These data do not support delayed initiation of rapamycin after IRI to attenuate IRI-induced progressive fibrosis and inflammation, and They raise further caution regarding rapamycin and albuminuria.
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PMID:Effects of delayed rapamycin treatment on renal fibrosis and inflammation in experimental ischemia reperfusion injury. 2000 42