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评估暴露于原卟啉Ⅸ介导的光动力疗法的巨噬细胞中的细胞损伤以及细胞因子肿瘤坏死因子-α、白细胞介素-6和白细胞介素-10的调节情况。

Evaluation of cell damage and modulation of cytokines TNF-α, IL-6 and IL-10 in macrophages exposed to PpIX-mediated photodynamic therapy.

作者信息

Tiveron R D R, Costa D A, Leite M D I, Vaz C B S, Sousa M, Carlos S M C F, Oliveira C J F, Machado R R, Paulino T P

机构信息

Núcleo de Biotérios, Biotério Central, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brasil.

Universidade de Uberaba, Uberaba, MG, Brasil.

出版信息

Braz J Biol. 2020 Sep;80(3):497-505. doi: 10.1590/1519-6984.193748. Epub 2019 Sep 26.

Abstract

Little is known regarding whether photodynamic therapy (PDT)-induced cell death can substantially compromise macrophages (MΦ), which are important cells in PDT-induced immune responses. Here, parameters of PDT-mediated MΦ cytotoxicity and cytokine production in response to protoporphyrin IX (PpIX) were evaluated. Peritoneal MΦ from BALB/c mice were stimulated in vitro with PDT, light, PpIX, or lipopolysaccharide (LPS). After that, cell viability, lipid peroxidation, Nitric Oxide (NO), DNA damage, TNF-α, IL-6 and IL-10 were evaluated. Short PDT exposure reduced cell viability by 10-30%. There was a two-fold increase in NO and DNA degradation, despite the non-increase in lipoperoxidation. PDT increased TNF-α and IL-10, particularly in the presence of LPS, and decreased the production of IL-6 to 10-fold. PDT causes cellular stress, induces NO radicals and leads to DNA degradation, generating a cytotoxic microenvironment. Furthermore, PDT modulates pro- and anti-inflammatory cytokines in MΦ.

摘要

关于光动力疗法(PDT)诱导的细胞死亡是否会严重损害巨噬细胞(MΦ),人们知之甚少,而巨噬细胞是PDT诱导的免疫反应中的重要细胞。在此,评估了PDT介导的MΦ细胞毒性参数以及对原卟啉IX(PpIX)产生的细胞因子。用PDT、光、PpIX或脂多糖(LPS)在体外刺激来自BALB/c小鼠的腹腔MΦ。之后,评估细胞活力、脂质过氧化、一氧化氮(NO)、DNA损伤、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)。短时间PDT照射使细胞活力降低了10%-30%。尽管脂质过氧化没有增加,但NO和DNA降解增加了两倍。PDT增加了TNF-α和IL-10,尤其是在存在LPS的情况下,并使IL-6的产生减少到原来的十分之一。PDT会导致细胞应激,诱导NO自由基并导致DNA降解,从而产生细胞毒性微环境。此外,PDT会调节MΦ中的促炎和抗炎细胞因子。

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