Kim Y S, Zheng S, Yang S H, Kim H L, Lim C S, Chae D W, Chun R, Lee J S, Kim S
Seoul National University Hospital, Seoul National University College of Medicine.
Clin Nephrol. 2001 Sep;56(3):199-206.
Intraglomerular cellular proliferation is one of the major determinants for dividing various glomerulonephritis (GN) into two groups, such as proliferative versus non-proliferative. Cytokines and chemokines are involved in the pathogenetic pathways and would affect the functional and histologic sequelae. We hypothesized that the morphological difference might be based on the differential intrarenal expression of various cytokines and chemokines. We quantified the intrarenal gene expression of various cytokines and chemokines, and correlated it with clinical parameters.
Total RNA was extracted from 54 proliferative GN (PGN) core biopsy specimens and 42 non-proliferative GN (NPGN) specimens. Using the internal competitors, RT-PCR was instituted to quantify mRNAs.
The magnitude of the gene expressions of IL-2, IFN-gamma, and IFN-gamma/IL-10 ratio were significantly higher in PGN than in NPGN. RANTES and IL-8 had more abundant gene messages in PGN. It was shown that Th1 cytokine was upregulated if GN was mediated by immune complexes regardless of cellular proliferation. But chemokines had the elevated levels of expression in PGN among immune complex-mediated GN. Up-regulation of the IFN-gamma/IL-10 ratio and TNF-alpha was associated with poor renal function at the time of biopsy. Renal tissues from the patients with a non-nephrotic range of proteinuria showed abundant messages for proinflammatory cytokines and chemokines.
Th1, proinflammatory cytokines, and chemokines were more abundant in proliferative GN, and correlated with unfavorable clinical parameters. We propose that the clinical manifestations and diverse histologic features of human GN are associated with differential expressions of specific cytokines and chemokines.
肾小球内细胞增殖是将各种肾小球肾炎（GN）分为两组的主要决定因素之一，如增殖性与非增殖性。细胞因子和趋化因子参与发病机制途径，并会影响功能和组织学后遗症。我们假设形态学差异可能基于各种细胞因子和趋化因子在肾内的差异表达。我们对各种细胞因子和趋化因子的肾内基因表达进行了定量，并将其与临床参数相关联。
从54例增殖性GN（PGN）核心活检标本和42例非增殖性GN（NPGN）标本中提取总RNA。使用内部竞争物，采用逆转录聚合酶链反应（RT-PCR）对mRNA进行定量。
PGN中IL-2、干扰素-γ（IFN-γ）的基因表达量以及IFN-γ/白细胞介素-10（IL-10）比值显著高于NPGN。PGN中调节激活正常T细胞表达和分泌因子（RANTES）和白细胞介素-8（IL-8）的基因信息更为丰富。结果表明，无论细胞增殖情况如何，若GN由免疫复合物介导，则Th1细胞因子上调。但在免疫复合物介导的GN中，趋化因子在PGN中的表达水平升高。活检时IFN-γ/IL-10比值和肿瘤坏死因子-α（TNF-α）的上调与肾功能不佳相关。蛋白尿未达到肾病范围的患者的肾组织显示促炎细胞因子和趋化因子的信息丰富。
Th1、促炎细胞因子和趋化因子在增殖性GN中更为丰富，并与不良临床参数相关。我们提出，人类GN的临床表现和多样的组织学特征与特定细胞因子和趋化因子的差异表达有关。
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