Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by oxidative stress and NF-kappaB.

Abstract

BACKGROUND:

Renal ischemia/reperfusion injury is a major cause of acute renal failure in both native kidneys and renal allografts. One important feature of such injury is monocyte/macrophage infiltration into the renal tissue. The infiltration of monocytes/macrophages can be induced by chemotactic factors produced by renal cells. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant protein for monocyte recruitment. The objective of the present study was to investigate mechanisms of elevated MCP-1 expression in rat kidney during ischemia/reperfusion injury.

METHODS:

The left kidney was subjected to one hour of ischemia followed by reperfusion for various time periods. The expression of MCP-1 mRNA was determined by nuclease protection assay and MCP-1 protein was identified by immunohistochemistry. Activation of a nuclear factor-kappa B (NF-kappaB) was determined by electrophoretic mobility shift assay and the level of lipid peroxides in the kidney was measured.

RESULTS:

There was a significant increase in MCP-1 expression in the ischemia/reperfusion kidney 2 hours after reperfusion (210% of the control). This increase was accompanied by activation of NF-kappaB, suggesting that this transcription factor might be involved in the event. The number of monocytes was significantly elevated in the kidney 3 days after ischemia/reperfusion. Pretreatment of rats with NF-kappaB inhibitors not only prevented NF-kappaB activation induced by ischemia/reperfusion, but also inhibited MCP-1 mRNA expression. Further analysis revealed that oxidative stress and increased IkappaB-alpha phosphorylation might be an underlying mechanism for NF-kappaB activation and subsequent MCP-1 mRNA expression in the ischemia/reperfusion kidney.

CONCLUSION:

The present study clearly demonstrates that enhanced MCP-1 expression in rat kidney during ischemia/reperfusion injury is mediated by NF-kappaB activation and oxidative stress. Elevated MCP-1 expression might be responsible for increased monocyte infiltration in the injured kidney.

• Authors: Fion L Sung, Tong Y Zhu, Kathy K W Au-Yeung, Yaw L Siow, Karmin O
• Journal: Kidney international (Kidney Int) Vol. 62 Issue 4 Pg. 1160-70 (Oct 2002) ISSN: 0085-2538 [Print] United States
• PMID: 12234286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL2
• I-kappa B Proteins
• NF-kappa B
• Nfkbia protein, rat
• NF-KappaB Inhibitor alpha

Topics

• Animals
• Chemokine CCL2 (genetics)
• Gene Expression (physiology)
• I-kappa B Proteins (genetics)
• Kidney (cytology, metabolism)
• Lipid Peroxidation (physiology)
• Male
• Monocytes (cytology)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Neutrophils (cytology)
• Oxidative Stress (physiology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, physiopathology)