Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury

Naoko Yokota, Melissa Burne-Taney, Lorraine C Racusen, Hamid Rabb

Research output: Contribution to journalArticle

Abstract

Recent data support a modulatory role for CD4 T cells in experimental renal ischemia-reperfusion injury (IRI). CD4 T cells can functionally differentiate to either a Th1 (IFN-γ producing) or the counterbalancing Th2 (IL-4) phenotype. The enzymes signal transducers and activators of transcription (STAT) 4 and STAT6 regulate Thl or Th2 differentiation and cytokine production, respectively. We therefore hypothesized that mice that were STAT4 deficient would be protected from renal IRI and that STAT6-deficient mice would have a more severe course. Intracellular cytokine staining of splenocytes from STAT4-/- or STAT6-/- exhibited distinct IFN-γ and IL-4 cytokine expression profiles. STAT6-/- had markedly worse renal function and tubular injury postischemia compared with wild type. STAT4-/- had only mildly improved function. Renal phagocyte infiltration and ICAM-1 upregulation were similar in STAT4-/-, STAT6-/-, and wild type. To evaluate if the mechanism of the marked worsening in the STAT6-/- mice could be due to IL-4 deficiency, IL-4-deficient mice were studied and had similar postischemic phenotype to STAT6-/- mice. These data demonstrate that the STAT6 pathway has a major protective role in renal IRI. IL-4 deficiency is a likely mechanism underlying the STAT6 effect. A "yin-yang" role for inflammation is emerging in renal IRI, similar to recent observations in atherosclerosis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume285
Issue number2 54-2
StatePublished - Aug 1 2003

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Reperfusion Injury
Signal Transduction
Interleukin-4
Kidney
Cytokines
STAT4 Transcription Factor
Yin-Yang
T-Lymphocytes
Phenotype
Intercellular Adhesion Molecule-1
Phagocytes
Atherosclerosis
Up-Regulation
Staining and Labeling
Inflammation
Wounds and Injuries
Enzymes

Keywords

  • Inflammation
  • Interleukin-4
  • Th1/Th2 cells

ASJC Scopus subject areas

  • Physiology

Cite this

Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury. / Yokota, Naoko; Burne-Taney, Melissa; Racusen, Lorraine C; Rabb, Hamid.

In: American Journal of Physiology - Renal Physiology, Vol. 285, No. 2 54-2, 01.08.2003.

Research output: Contribution to journalArticle

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