Ischemic acute tubular necrosis induces an extensive local cytokine response. Evidence for induction of interferon-gamma, transforming growth factor-beta 1, granulocyte-macrophage colony-stimulating factor, interleukin-2, and interleukin-10.
Ischemic acute tubular necrosis induces an extensive local cytokine response. Evidence for induction of interferon-gamma, transforming growth factor-beta 1, granulocyte-macrophage colony-stimulating factor, interleukin-2, and interleukin-10.
复制标题
缺血性急性肾小管坏死诱导广泛的局部细胞因子反应。
作者：
N. Goes;J. Urmson;V. Ramassar;P. Halloran
我们以前注意到缺血性急性肾小管坏死（ATN）诱导局部表达的MHC产物在肾上皮细胞。本研究旨在探讨IFN-γ对ATN中MHC抗原表达的调节作用以及缺血性肾损伤诱导的细胞因子和生长因子表达的变化。我们通过夹闭左肾蒂在小鼠中产生单侧缺血性ATN。通过北方印迹分析评估MHC I类和II类稳态mRNA诱导，并通过放射性标记的单克隆抗体与组织匀浆的结合程度定量MHC产物。通过逆转录聚合酶链反应评估IFN-γ、IL-2、IL-10和粒细胞-巨噬细胞CSF的稳态mRNA水平，通过北方印迹分析评估转化生长因子β 1和前表皮生长因子原（ppEGF）的水平。在损伤的肾脏中，IFN-γ、IL-2、IL-10、粒细胞-巨噬细胞CSF和转化生长因子β-1的稳态mRNA水平增加，而ppEGF mRNA显著降低。通过用抗IFN-γ mAb（R4 - 6A2）处理小鼠来抑制MHC表达。小鼠EGF，试图加速恢复，并没有减少细胞因子和MHC的变化。这些数据表明，缺血性损伤，可能还有其他形式的损伤，触发了一个复杂的促炎细胞因子回路。这种“损伤反应”可能与临床肾移植相关，其中ATN与移植物结局不良相关。
We noted previously that ischemic acute tubular necrosis (ATN) induces local expression of MHC products in renal epithelium. The present investigations were conducted to establish the role of IFN-gamma in the regulation of MHC antigen expression in ATN and to explore the changes in cytokine and growth factor expression induced by ischemic renal injury. We produced unilateral ischemic ATN in mice by clamping the left renal pedicle. MHC class I and II steady state mRNA induction was assessed by northern blot analysis, and MHC product was quantified by the extent of binding of radiolabeled monoclonals to tissue homogenates. The steady state mRNA levels for IFN-gamma, IL-2, IL-10, and granulocyte-macrophage CSF were assessed by reverse transcriptase polymerase chain reaction and the levels for transforming growth factor-beta 1 and prepro-epidermal growth factor (ppEGF) were assessed by Northern blot analysis. In the injured kidneys, steady state mRNA levels for IFN-gamma, IL-2, IL-10, granulocyte-macrophage CSF, and transforming growth factor beta-1 were increased, whereas ppEGF mRNA was markedly decreased. The MHC expression was inhibited by treatment of mice with an anti-IFN-gamma mAb (R4-6A2). Murine EGF, administered in an attempt to accelerate recovery, did not reduce the cytokine and MHC changes. These data indicate that ischemic injury, and possibly other forms of injury, triggers a complex circuit of proinflammatory cytokines. This "injury response" could be relevant to clinical renal transplants, where ATN is associated with poor graft outcome.