title: Chemokine expression in renal ischemia/reperfusion injury is most profound during the reparative phase.
abstract: Chemokines are important players in the migration of leukocytes to sites of injury and are also involved in angiogenesis, development and wound healing. In this study, we performed microarray analyses to identify chemokines that play a role during the inflammatory and repair phase after renal ischemia/reperfusion (I/R) injury and investigated the temporal relationship between chemokine expression, leukocyte accumulation and renal damage/repair. C57Bl/6 mice were subjected to unilateral ischemia for 45 min and sacrificed 3 h, 1 day and 7 days after reperfusion. From ischemic and contralateral kidney, RNA was isolated and hybridized to a microarray. Microarray results were validated with quantitative real-time reverse transcription-PCR (QRT-PCR) on RNA from an independent experiment. (Immuno)histochemical analyses were performed to determine renal damage/repair and influx of leukocytes. Twenty out of 114 genes were up-regulated at one or more reperfusion periods. All these genes were up-regulated 7 days after I/R. Up-regulated genes included CC chemokines MCP-1 and TARC, CXC chemokines KC and MIP-2alpha, chemokine receptors Ccr1 and Cx3cr1 and related genes like matrix metalloproteinases. Microarray data of 1 and 7 days were confirmed for 17 up-regulated genes by QRT-PCR. (Immuno)histochemical analysis showed that the inflammatory and repair phase after renal I/R injury take place after, respectively, 1 and 7 days. Interestingly, chemokine expression was highest during the repair phase. In addition, expression profiles showed a biphasic expression of all up-regulated CXC chemokines coinciding with the early inflammatory and late repair phase. In conclusion, we propose that temporal expression of chemokines is a crucial factor in the regulation of renal I/R injury and repair.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands. i.stroo@amc.uva.nl <i.stroo@amc.uva.nl>
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.forename: Geurt
authors.initials: G
authors.lastname: Stokman
authors.forename: Gwen J D
authors.initials: GJ
authors.lastname: Teske
authors.forename: Anje
authors.initials: A
authors.lastname: Raven
authors.forename: Loes M
authors.initials: LM
authors.lastname: Butter
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
mesh_terms: D000818:Animals; D002452:Cell Count; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007120:Immunochemistry; D007249:Inflammation; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009504:Neutrophils / Q000473:pathology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine
references.citation: J Am Soc Nephrol. 2003 Apr;14(4):1066-71
references.pmid: 12660342
references.citation: Pharmacol Ther. 2006 Oct;112(1):139-49
references.pmid: 16720046
references.citation: Am Fam Physician. 2000 Apr 1;61(7):2077-88
references.pmid: 10779250
references.citation: Nephron Exp Nephrol. 2008;109(1):c29-38
references.pmid: 18520167
references.citation: Am J Physiol. 1989 May;256(5 Pt 2):F794-802
references.pmid: 2541628
references.citation: J Am Soc Nephrol. 2003 Oct;14(10):2503-15
references.pmid: 14514728
references.citation: Kidney Int. 1998 Mar;53(3):726-34
references.pmid: 9507220
references.citation: Am J Physiol. 1991 Dec;261(6 Pt 2):F1095-101
references.pmid: 1750520
references.citation: Arthritis Rheum. 2003 Sep;48(9):2555-66
references.pmid: 13130475
references.citation: J Am Soc Nephrol. 2000 Jan;11(1):152-176
references.pmid: 10616852
references.citation: J Am Soc Nephrol. 2006 Mar;17(3):716-23
references.pmid: 16481416
references.citation: Am J Physiol Renal Physiol. 2004 Mar;286(3):F581-9
references.pmid: 14600031
references.citation: Methods Mol Biol. 2000;132:365-86
references.pmid: 10547847
references.citation: J Clin Invest. 2005 Oct;115(10):2894-903
references.pmid: 16167081
references.citation: J Am Soc Nephrol. 2006 Feb;17(2):454-64
references.pmid: 16382019
references.citation: Kidney Int. 2003 Feb;63(2):401-15
references.pmid: 12631106
references.citation: Arthritis Rheum. 2005 May;52(5):1522-33
references.pmid: 15880599
references.citation: Kidney Int. 2009 Mar;75(5):526-35
references.pmid: 19092796
references.citation: Am J Physiol Renal Physiol. 2008 Jan;294(1):F264-71
references.pmid: 18003857
references.citation: J Leukoc Biol. 2006 Jan;79(1):114-22
references.pmid: 16275892
references.citation: Cell Immunol. 2007 Jul;248(1):4-11
references.pmid: 17942086
references.citation: J Am Soc Nephrol. 2005 Jun;16(6):1684-92
references.pmid: 15829714
references.citation: J Immunol. 1995 Jun 1;154(11):6048-57
references.pmid: 7751647
references.citation: Am J Pathol. 2006 Aug;169(2):372-87
references.pmid: 16877340
references.citation: Eur J Immunol. 2004 Jun;34(6):1617-26
references.pmid: 15162431
references.citation: Diabetologia. 2007 Feb;50(2):471-80
references.pmid: 17160673
references.citation: J Hypertens. 1997 Dec;15(12 Pt 1):1365-77
references.pmid: 9431840
references.citation: Eur J Immunol. 2002 Jul;32(7):2037-45
references.pmid: 12115625
references.citation: Leukemia. 2008 Mar;22(3):466-73
references.pmid: 17972941
references.citation: Am J Pathol. 2001 Dec;159(6):2137-45
references.pmid: 11733364
references.citation: J Pathol. 2008 Jan;214(1):104-13
references.pmid: 17973244
references.citation: Cell Mol Immunol. 2004 Apr;1(2):95-104
references.pmid: 16212895
references.citation: J Am Soc Nephrol. 2005 Jul;16(7):2034-43
references.pmid: 15901765
references.citation: PLoS One. 2008;3(10):e3596
references.pmid: 18974879
references.citation: Kidney Int. 2006 Jan;69(1):73-80
references.pmid: 16374426
references.citation: Eur J Immunol. 2002 Nov;32(11):3197-205
references.pmid: 12555665
references.citation: Immunol Rev. 2000 Oct;177:195-203
references.pmid: 11138776
references.citation: J Clin Invest. 2008 Nov;118(11):3522-30
references.pmid: 18982158
references.citation: N Engl J Med. 2006 Feb 9;354(6):610-21
references.pmid: 16467548
references.citation: J Exp Med. 1998 Feb 16;187(4):601-8
references.pmid: 9463410
references.citation: Annu Rev Immunol. 2000;18:217-42
references.pmid: 10837058
references.citation: Rheumatology (Oxford). 2004 Sep;43(9):1121-8
references.pmid: 15213333
references.citation: FASEB J. 1999 Sep;13(12):1565-74
references.pmid: 10463948
references.citation: J Am Soc Nephrol. 2006 Jan;17(1):131-40
references.pmid: 16291841
references.citation: J Leukoc Biol. 1995 Sep;58(3):359-64
references.pmid: 7665992
references.citation: Curr Pharm Des. 2006;12(23):2923-34
references.pmid: 16918422
references.citation: Neurosci Lett. 2003 Mar 13;339(1):62-6
references.pmid: 12618301
references.citation: Aliment Pharmacol Ther. 2000 Apr;14 Suppl 1:94-100
references.pmid: 10807410