Influence of TH1/TH2 switched immune response on renal ischemia-reperfusion injury

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Marques‚ V.P. ; Gonçalves‚ G.M. ; Feitoza‚ C.Q. ; Cenedeze‚ M.A. ; Fernandes Bertocchi‚ A.P. ; Damiao‚ M.J. ; Pinheiro‚ H.S. ; Antunes Teixeira‚ V.P. ; dos Reis‚ M.A. ; Pacheco-Silva‚ A. ; others

• Document type: Journal article
• Source: NEPHRON EXPERIMENTAL NEPHROLOGY; v. 104, n. 1, p. e48-e56, 2006.

Abstract

Background/Aims: Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1). Methods: We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24,48 and 120 h after surgery. Results/Conclusions: The IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. The IL-12-deficient mice were not affected. The IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. The IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1. Copyright (c) 2006 S. Karger AG, Basel. (AU)

• FAPESP's process: 04/08311-6 - Molecular, cellular and pathophysiological mechanisms on acute renal failure
• Grantee: Nestor Schor
• Support Opportunities: Research Projects - Thematic Grants