| First Author | Yokota N | Year | 2003 |
| Journal | Am J Physiol Renal Physiol | Volume | 285 |
| Issue | 2 | Pages | F319-25 |
| PubMed ID | 12709397 | Mgi Jnum | J:84825 |
| Mgi Id | MGI:2670299 | Doi | 10.1152/ajprenal.00432.2002 |
| Citation | Yokota N, et al. (2003) Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 285(2):F319-25 |
| abstractText | 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-gamma producing) or the counterbalancing Th2 (IL-4) phenotype. The enzymes signal transducers and activators of transcription (STAT) 4 and STAT6 regulate Th1 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-gamma 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. |
