Salmonella‑induced miR‑155 enhances necroptotic death in macrophage cells via targeting RIP1/3

沙门氏菌诱导的 miR-155 通过靶向 RIP1/3 增强巨噬细胞坏死性死亡

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作者:Young-Tae Ro, Guk-Heui Jo, Sun-Ah Jung, Eunjoo H Lee, Jongdae Shin, Joon H Lee

Abstract

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.

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