Shiga toxin-1 regulation of cytokine production by human glomerular epithelial cells.
Shiga toxin-1 regulation of cytokine production by human glomerular epithelial cells.
复制标题
Shiga toxin-1 对人肾小球上皮细胞细胞因子产生的调节。
作者：
Hughes,AK;Stricklett,PK;Kohan,DE
背景/目的：炎症细胞因子可能通过增强志贺毒素（Stx）的细胞毒性作用来增强腹泻后溶血性尿毒症综合征（Stx HUS）的肾损伤。 Stx HUS 中炎症细胞因子的来源尚不清楚。由于 Stx-1 有效抑制肾小球上皮细胞 (GEC) 的蛋白质合成并增加肾上皮细胞的细胞因子释放，因此我们研究了 Stx-1 对人 GEC 产生细胞因子的调节。方法：测定了 Stx-1（和另一种蛋白质合成抑制剂放线菌酮 (CHX)）的细胞毒性、蛋白质合成抑制以及对白细胞介素 1 (IL-1)、白细胞介素 6 (IL-6) 和肿瘤坏死因子 (TNF) 释放和 mRNA 水平的影响。结果：Stx-1 单独对 GEC 产生炎症细胞因子具有适度的刺激作用，这种作用在毒素浓度范围从最小到 50% 的蛋白质合成抑制时发生。 CHX 在对蛋白质合成产生类似抑制作用的浓度下，增加了 IL-1、IL-6 和 TNF 蛋白质的释放和 mRNA 的积累，但其时间和剂量依赖性模式与 Stx 不同。脂多糖 (LPS) 不会改变 IL-1，但会刺激 IL-6 和 TNF 的产生。 LPS 和 Stx-1 联合刺激所有三种细胞因子的产生，其程度比单独使用任何一种毒素更大。结论：这些数据表明：(1) Stx-1 单独适度刺激 GEC 炎症细胞因子的产生；(2) LPS 和 Stx-1 联合使用可以有效增强 GEC 细胞因子的释放，(3) Stx-1 的这种作用可能部分与抑制蛋白质合成有关，但不能完全归因于这种作用。
Background/Aims: Inflammatory cytokines may enhance renal injury in post-diarrheal hemolytic uremic syndrome (Stx HUS) by enhancing the cytotoxic effect of Shiga toxins (Stx). The sources of inflammatory cytokines in Stx HUS are unclear. Since Stx-1 potently inhibits protein synthesis by glomerular epithelial cells (GEC) and increases cytokine release by renal epithelial cells, we examined Stx-1 regulation of cytokine production by human GEC. Methods: Stx-1 (and cycloheximide (CHX), another protein synthesis inhibitor) cytotoxicity, protein synthesis inhibition, and effect on interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) release and mRNA levels were determined. Results: Stx-1 alone had a modest stimulatory effect on inflammatory cytokine production by GEC that occurred at toxin concentrations ranging from minimal to 50% inhibition of protein synthesis. CHX, at concentrations that produced similar inhibition of protein synthesis, increased IL-1, IL-6, and TNF protein release and mRNA accumulation, but in a different time-and dose-dependent pattern than Stx. Lipopolysaccharide (LPS) did not change IL-1, but stimulated IL-6 and TNF production. LPS and Stx-1 combined stimulated production of all three cytokines to a greater extent than either toxin alone. Conclusion: These data indicate that:(1) Stx-1 alone modestly stimulates GEC inflammatory cytokine production;(2) LPS and Stx-1 combined can potently enhance GEC cytokine release, and (3) this action of Stx-1 may relate in part to inhibition of protein synthesis but cannot be fully attributed to this effect.