Chemokine expression in experimental tubulointerstitial nephritis.
Chemokine expression in experimental tubulointerstitial nephritis.
复制标题
实验性肾小管间质性肾炎中趋化因子的表达。
作者：
Winson W. Tang;M. Qi;J. Warren;G. Van
趋化因子可能在肾小球疾病相关的肾小管间质性肾炎中白细胞浸润的发病机制中起重要作用。我们研究了肾皮质C-C表达，（巨噬细胞炎性蛋白-1 α（MIP-1 α））、单核细胞趋化蛋白-1（MCP-1）和RANTES）和C-X-C（干扰素诱导蛋白-10（IP-10），MIP-2，和嘌呤诱导的中性粒细胞趋化因子（CINC））趋化因子4，6，8，10，14，在嘌呤霉素氨基糖苷（PAN）肾病诱导后21天。在给予PAN后6至8天，大鼠肾皮质中IP-10和MCP-1的稳态mRNA表达增加7至10倍，此后下降，到第21天达到对照值。IP-10和MCP-1 mRNA的产生定位于固有的肾小管间质细胞，而不是浸润的单核细胞或巨噬细胞。相比之下，有一个低的基础表达RANTES mRNA在肾病大鼠的肾皮质，并没有不同于对照组大鼠。相反，未检测到CINC、MIP-2和MIP-1 α mRNA。用ELISA证实MCP-1 mRNA翻译成蛋白质。趋化因子基因表达的这些变化与肾小管间质T淋巴细胞和巨噬细胞浸润相关，从第6天开始，在第10天达到峰值。从第4天开始对大鼠MCP-1（n = 5）施用中和Ab导致肾小管间质巨噬细胞浸润从8.4 +/-1.3%下降45%至第6天的4.6 +/-0.4%（p < 0.001）。这些数据提供的证据表明，MCP-1，可能IP-10，是重要的发病机制中的单核细胞/巨噬细胞浸润的肾小管间质性肾炎与PAN肾病。
Chemokines may be important in the pathogenesis of leukocyte infiltration in tubulointerstitial nephritis associated with glomerular disease. We studied the renal cortical expression of the C-C (macrophage inflammatory protein-1alpha (MIP-1alpha)), monocyte chemotactic protein-1 (MCP-1), and RANTES) and C-X-C (interferon-inducible protein-10 (IP-10), MIP-2, and cytokine-induced neutrophil chemoattractant (CINC)) chemokines 4, 6, 8, 10, 14, and 21 days after the induction of puromycin aminonucleoside (PAN) nephrosis. There was a 7- to 10-fold increase in the steady state mRNA expression of IP-10 and MCP-1 in the renal cortex of rats 6 to 8 days after the administration of PAN that declines thereafter reaching control values by day 21. The site of IP-10 and MCP-1 mRNA production was localized to intrinsic tubulointerstitial cells and not to infiltrating monocytes or macrophages. By comparison, there was a low basal expression of RANTES mRNA in the renal cortex of nephrotic rats that did not differ from those of control rats. In contrast, CINC, MIP-2, and MIP-1alpha mRNAs were not detected. Translation of MCP-1 mRNA into protein was confirmed with an ELISA. These changes in chemokine gene expression were associated with a tubulointerstitial T lymphocyte and macrophage infiltration beginning on day 6 that peaked on day 10. Administration of a neutralizing Ab to rat MCP-1 (n = 5) beginning on day 4 resulted in a 45% decline in tubulointerstitial macrophage infiltration from 8.4 +/- 1.3% to 4.6 +/- 0.4% (p < 0.001) on day 6. These data provide evidence that MCP-1, and possibly IP-10, are important in the pathogenesis of monocyte/macrophage infiltration in the tubulointerstitial nephritis associated with PAN nephrosis.