Prominent and sustained up-regulation of gp130-signaling cytokines and the chemokine MIP-2 in murine renal ischemia-reperfusion injury.
Ischemia-reperfusion injury (IRI) is a major cause of renal dysfunction in both native kidneys and renal allografts. To broaden our understanding of the inflammatory mediators involved in IRI, we used multi-probe RNase protection assays to examine the expression of 26 different cytokine genes in a murine model of renal IRI. We observed that, in addition to up-regulation of IL-1beta and to a lesser extent TNF-alpha, IRI was associated with an intense and sustained up-regulation of three gp130-signaling cytokines, IL-6, IL-11, and leukemia inhibitory factor (LIF), as well as with up-regulation of the neutrophil chemotactic and activating mediator macrophage inflammatory protein (MIP)-2. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein (MCP)-1 were also moderately up-regulated after IRI, whereas mRNA levels of several other inflammatory mediators including IL-1alpha, IL-2, IL-4, interferon (IFN)-gamma, GM-CSF, and RANTES were minimally increased or remained undetectable. These findings identify MIP-2 as an attractive target for inhibition of leukocyte recruitment in renal IRI and also suggest a potentially novel role for gp130-mediated signals in IRI.
Lemay
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S
Division of Nephrology, New England Medical Center, Boston, Massachusetts 02111, USA.
Rabb
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H
Postler
G
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Singh
A K
AK
D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006131:Growth Inhibitors / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D017370:Interleukin-11 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D006131:Growth Inhibitors; D018836:Inflammation Mediators; D017370:Interleukin-11; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins