Prominent and sustained up-regulation of gp130-signaling cytokines and the chemokine MIP-2 in murine renal ischemia-reperfusion injury

Transplantation. 2000 Mar 15;69(5):959-63. doi: 10.1097/00007890-200003150-00049.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokine CXCL2
  • Chemokines / metabolism*
  • Cytokines / metabolism*
  • Growth Inhibitors / metabolism
  • Inflammation Mediators / metabolism
  • Interleukin-11 / metabolism
  • Interleukin-6 / metabolism
  • Ischemia / metabolism*
  • Leukemia Inhibitory Factor
  • Lymphokines / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Renal Circulation*
  • Reperfusion Injury / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Cytokines
  • Growth Inhibitors
  • Inflammation Mediators
  • Interleukin-11
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Lymphokines
  • Membrane Glycoproteins