Laboratory of Biochemistry, Graduate School of Medicine, Konkuk University, Chungju, Chungcheong 27478, Republic of Korea.
Laboratory of Cell Biology, Myunggok Eye Research Institute, Konyang University College of Medicine, Seoul 07301, Republic of Korea.
Mol Med Rep. 2018 Dec;18(6):5133-5140. doi: 10.3892/mmr.2018.9525. Epub 2018 Oct 1.
Salmonella enterica serovar Typhimurium (hereafter referred to as Salmonella), a virulent pathogen, is known to induce host‑cell death. Using reverse transcription‑quantitative polymerase chain reaction, a 28‑fold increase of microRNA (miR)‑155 expression in RAW 264.7 macrophages was observed following infection with Salmonella for 24 h. This miR‑155 upregulation increased macrophage cell death by up to 40% in 48 h following infection. Western blot analysis revealed that receptor interacting protein 1 (RIP1) and 3 (RIP3) were increased at 18 h following miR‑155 transfection to macrophages, similar to Salmonella infection. In addition, inhibition of RIP1 by pre‑incubating macrophages with necrostatin‑1, a RIP1 specific inhibitor, increased the viability of Salmonella‑infected cells and miR‑155‑transfected cells by up to 20%. The cleavage of poly (adenosine diphosphate‑ribose) polymerase‑1 (PARP‑1) was also enhanced by miR‑155 induction upon Salmonella infection. Therefore, it was suggested that RIP1/3‑induced necroptosis and PARP‑1‑mediated necrosis caused by miR‑155 induction may represent distinct routes of programmed necrotic cell death of Salmonella‑infected macrophages.
鼠伤寒沙门氏菌（以下简称沙门氏菌）是一种毒力病原体，已知会诱导宿主细胞死亡。通过逆转录定量聚合酶链反应，在沙门氏菌感染 RAW 264.7 巨噬细胞 24 小时后，观察到 microRNA（miR）-155 的表达增加了 28 倍。这种 miR-155 的上调使感染后 48 小时内巨噬细胞的死亡增加了 40%。Western blot 分析显示，在 miR-155 转染巨噬细胞后 18 小时，受体相互作用蛋白 1（RIP1）和 3（RIP3）增加，类似于沙门氏菌感染。此外，通过用 necrostatin-1（一种 RIP1 特异性抑制剂）预先孵育巨噬细胞来抑制 RIP1，可使沙门氏菌感染细胞和 miR-155 转染细胞的存活率提高多达 20%。miR-155 诱导也增强了沙门氏菌感染时多聚（腺苷二磷酸核糖）聚合酶-1（PARP-1）的切割。因此，据推测，RIP1/3 诱导的坏死和 miR-155 诱导的 PARP-1 介导的坏死可能代表沙门氏菌感染巨噬细胞程序性坏死的不同途径。
