Acencio Milena Marques Pagliarelli, Silva Bruna Rocha, Teixeira Lisete Ribeiro, Alvarenga Vanessa Adélia, Silva Carlos Sérgio Rocha, da Silva Aline Graças Pereira, Capelozzi Vera Luiza, Marchi Evaldo
Laboratorio de Pleura-Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Department of Pathology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Oncotarget. 2020 Oct 13;11(41):3730-3736. doi: 10.18632/oncotarget.27750.
Introdution: To determine the role of Pleural Mesothelial Cells (PMC) and/or Neoplasic Cells (NC) in the initiation and regulation of acute inflammatory response after exposure to talc for evaluating inflammatory mediators and cellular alterations.
PMC cultures, human lung (A549) and breast (MCF7) adenocarcinoma cells were divided in 5 groups: 100% PMC, 100% NC, 25% PMC + 75% NC, 50% of each type and 75% PMC + 25% NC. All groups were exposed to talc and measured IL-6, IL-1β, IL-10, TNF-α, TNFRI, pH, LDH, apoptosis and necrosis.
One-way Anova.
High IL-6, IL-1β and TNFRI levels were found in PMC and NC exposed to talc. IL-6 was higher at the points of more confluence of PMC. The highest levels of IL-1β and TNFRI were found in mixed cultures. In pure cultures TNFRI was higher in A549 followed by PMC and MCF7. LDH was higher in A549 than PMC. The lowest pH was found in 100% NC. All cell line exposed to talc reduced viability and increased necrosis. Apoptotic cells exposed to talc were higher in pure cultures of NC than in PMC. Mixed cultures of PMC and A549 showed lower levels of apoptosis in cultures with more NC.
PMC after talc exposure participates in the inflammatory process contributing to production of molecular mediators, necessary for effective pleurodesis. Talc acted in NC causing higher rates of apoptosis, contributing in a modest way to tumoral decrease. Different types of tumor cells may respond differently to exposure to talc.
为了确定胸膜间皮细胞(PMC)和/或肿瘤细胞(NC)在接触滑石粉后急性炎症反应的起始和调节中的作用,以评估炎症介质和细胞改变。
PMC培养物、人肺(A549)和乳腺(MCF7)腺癌细胞分为5组:100% PMC、100% NC、25% PMC + 75% NC、每种类型各50%以及75% PMC + 25% NC。所有组均接触滑石粉,并检测白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、肿瘤坏死因子受体I(TNFRI)、pH值、乳酸脱氢酶(LDH)、凋亡和坏死情况。
单因素方差分析。
接触滑石粉的PMC和NC中发现IL-6、IL-1β和TNFRI水平较高。在PMC汇合度更高的时间点,IL-6水平更高。混合培养物中发现IL-1β和TNFRI水平最高。在纯培养物中,A549中的TNFRI水平高于PMC和MCF7。A549中的LDH高于PMC。100% NC中的pH值最低。所有接触滑石粉的细胞系活力均降低,坏死增加。接触滑石粉的凋亡细胞在NC纯培养物中高于PMC。PMC和A549的混合培养物在NC较多的培养物中凋亡水平较低。
接触滑石粉后的PMC参与炎症过程,有助于产生有效胸膜固定术所需的分子介质。滑石粉作用于NC导致更高的凋亡率,对肿瘤缩小有一定贡献。不同类型的肿瘤细胞对接触滑石粉的反应可能不同。