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Effects of Escherichia Coli subtilase cytotoxin and shiga toxin 2 on primary cultures of human renal tubular epithelial cells

机译：大肠杆菌枯草杆菌蛋白酶细胞毒素和志贺毒素2对人肾小管上皮细胞原代培养的影响

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Shiga toxin (Stx)-producing Escherichia coli (STEC) cause post-diarrhea Hemolytic Uremic Syndrome (HUS), which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB) that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC) and compare its effects with those produced by Shiga toxin type 2 (Stx2), in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2.
机译：产生志贺毒素（Stx）的大肠杆菌（STEC）引起腹泻后溶血性尿毒综合症（HUS），这是世界许多地方儿童急性肾衰竭的最常见原因。几种非O157 STEC菌株还产生枯草杆菌蛋白酶，可能导致HUS发病。本工作的目的是研究SubAB对人肾皮质肾小管上皮细胞（HRTEC）的原代培养的细胞毒性作用，并将其作用与2型志贺毒素产生的作用进行比较，以评估其对2型志贺毒素的影响。 HUS中的肾损伤。为了这个目的，在与SubAB和/或Stx2毒素一起孵育的HRTEC上测定细胞活力，增殖速率和凋亡。 SubAB显着降低了细胞活力和细胞增殖速率，并以时间依赖性方式刺激了HRTEC培养物中的细胞凋亡。但是，HRTEC培养物对Stx2的细胞毒性作用比SubAB产生的敏感性高得多。将HRTEC与SubAB和Stx2共同孵育时，未观察到协同作用。将HRTEC与灭活的SubAA272B毒素孵育后，结果与未处理的对照细胞相似。与HRTEC相比，在与SubAB或/和Stx2孵育的Vero细胞中观察到了类似的凋亡刺激。总之，尽管与Stx2相比，HRTEC的原代培养对SubAB的细胞毒性作用非常敏感。

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