Gerritsma J S, Gerritsen A F, Van Kooten C, Van Es L A, Daha M R
Department of Nephrology, Leiden University Hospital, The Netherlands.
Mol Immunol. 1996 Jul;33(10):847-54. doi: 10.1016/0161-5890(96)84610-4.
Local production in tubular cells of complement has been shown to occur in several kidney diseases by in situ hybridization, but the regulation at the local site during an inflammation is still unknown. In the present study, we demonstrate that human proximal tubular epithelial cells (PTEC) are able to produce complement components C3 and Factor B under non-stimulated conditions in vitro. The basal production of both was increased by 0.5 ng/ml interleukin-1 alpha (IL-1 alpha) for C3: from 95.5 +/- 4.0 ng/10(6) cells to 416.5 +/- 4.9 ng/10(6), and for Factor B: from 271 +/- 7.0 ng/10(6) cells to 457.5 +/- 7.0 ng/10(6) cells. In contrast cytokines such as TNF-alpha, IFN-gamma, IL-10 and IL-15 had no detectable effect. The upregulation by IL-1 alpha was dose- and time-dependent. The response to IL-1 alpha was shown to be mediated via the IL-1 receptor, as the addition of recombinant interleukin-1 receptor antagonist inhibited the IL-1 alpha induced complement production by more than 80%. IL-1 alpha enhanced mRNA expression of both C3 and Factor B as demonstrated by RT-PCR and dot-blot analysis. This indicated that IL-1 alpha upregulated the expression of the C3 and Factor B at the transcriptional level. We hypothesize that in vivo the production of C3 and Factor B at the local site during an inflammatory response in the kidney may be regulated by IL-1 alpha produced by inflammatory cells.
通过原位杂交已证实在几种肾脏疾病中，肾小管细胞可进行补体的局部生成，但炎症期间局部位点的调节机制仍不清楚。在本研究中，我们证明人近端肾小管上皮细胞（PTEC）在体外非刺激条件下能够产生补体成分C3和B因子。二者的基础生成量在加入0.5 ng/ml白细胞介素-1α（IL-1α）后均增加，C3：从95.5±4.0 ng/10⁶细胞增加至416.5±4.9 ng/10⁶，B因子：从271±7.0 ng/10⁶细胞增加至457.5±7.0 ng/10⁶细胞。相比之下，细胞因子如肿瘤坏死因子-α、干扰素-γ、白细胞介素-10和白细胞介素-15未显示出可检测到的作用。IL-1α的上调呈剂量和时间依赖性。对IL-1α的反应显示是通过IL-1受体介导的，因为添加重组白细胞介素-1受体拮抗剂可抑制IL-1α诱导的补体生成达80%以上。逆转录聚合酶链反应（RT-PCR）和斑点印迹分析表明，IL-1α增强了C3和B因子的mRNA表达。这表明IL-1α在转录水平上调了C3和B因子的表达。我们推测，在体内，肾脏炎症反应期间局部位点C3和B因子的生成可能受炎症细胞产生的IL-1α调节。
