Rahman Mizanur, Sompa Shanzina Iasmin, Introna Micol, Upadhyay Swapna, Ganguly Koustav, Palmberg Lena
Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
J Inflamm (Lond). 2023 Nov 17;20(1):39. doi: 10.1186/s12950-023-00367-6.
Clinical cases and experimental evidence revealed that electronic cigarettes (ECIG) induce serious adverse health effects, but underlying mechanisms remain to be fully uncovered. Based on recent exploratory evidence, investigating the effects of ECIG on macrophages can broadly define potential mechanisms by focusing on the effect of ECIG exposure with or without nicotine. Here we investigated the effect of ECIG-aerosol exposure on macrophages (MQ) phenotype, inflammatory response, and function of macrophages.MQ were cultured at air liquid interface and exposed to ECIG-aerosol. Oxidative stress was determined by reactive oxygen species (ROS), heat shock protein 60 (HSP60), glutathione peroxidase (GPx) and heme oxygenase1 (HMOX1). Lipid accumulation and lipid peroxidation were defined by lipid staining and level of malondialdehyde (MDA) respectively. MQ polarization was identified by surface expression markers CD86, CD11C and CD206 as well as pro-inflammatory and anti-inflammatory cytokines in gene and protein level. Phagocytosis of E. coli by MQ was investigated by fluorescence-based phagocytosis assay.ECIG-aerosol exposure in presence or absence of nicotine induced oxidative stress evidenced by ROS, HSP60, GPx, GPx4 and HMOX1 upregulation in MQ. ECIG-aerosol exposure induced accumulation of lipids and the lipid peroxidation product MDA in MQ. Pro-inflammatory MQ (M1) markers CD86 and CD11C but not anti-inflammatory MQ (M2) marker CD206 were upregulated in response to ECIG-aerosol exposure. In addition, ECIG induced pro-inflammatory cytokines IL-1beta and IL-8 in gene level and IL-6, IL-8, and IL-1beta in protein level whereas ECIG exposure downregulated anti-inflammatory cytokine IL-10 in protein level. Phagocytosis activity of MQ was downregulated by ECIG exposure. shRNA mediated lipid scavenger receptor 'CD36' silencing inhibited ECIG-aerosol-induced pro-inflammatory MQ polarization and recovered phagocytic activity of MQ.ECIG exposure alters lung lipid homeostasis and thus induced inflammation by inducing M1 type MQ and impair phagocytic function, which could be a potential cause of ECIG-induced lung inflammation in healthy and inflammatory exacerbation in disease condition.
临床病例和实验证据表明，电子烟会引发严重的健康不良影响，但其潜在机制仍有待全面揭示。基于近期的探索性证据，通过聚焦有无尼古丁情况下电子烟暴露的影响来研究电子烟对巨噬细胞的作用，可大致明确潜在机制。在此，我们研究了电子烟气溶胶暴露对巨噬细胞（MQ）表型、炎症反应及巨噬细胞功能的影响。将MQ在气液界面培养并暴露于电子烟气溶胶中。通过活性氧（ROS）、热休克蛋白60（HSP60）、谷胱甘肽过氧化物酶（GPx）和血红素加氧酶1（HMOX1）来测定氧化应激。分别通过脂质染色和丙二醛（MDA）水平来界定脂质蓄积和脂质过氧化。通过表面表达标志物CD86、CD11C和CD206以及基因和蛋白水平的促炎和抗炎细胞因子来鉴定MQ极化。通过基于荧光的吞噬试验研究MQ对大肠杆菌的吞噬作用。有无尼古丁情况下的电子烟气溶胶暴露均诱导了氧化应激，表现为MQ中ROS、HSP60、GPx、GPx4和HMOX1上调。电子烟气溶胶暴露诱导了MQ中脂质蓄积及脂质过氧化产物MDA的产生。响应电子烟气溶胶暴露，促炎MQ（M1）标志物CD86和CD11C上调，而抗炎MQ（M2）标志物CD206未上调。此外，电子烟在基因水平诱导促炎细胞因子IL-1β和IL-8，在蛋白水平诱导IL-6、IL-8和IL-1β，而电子烟暴露在蛋白水平下调抗炎细胞因子IL-10。电子烟暴露下调了MQ的吞噬活性。短发夹RNA介导的脂质清道夫受体“CD36”沉默抑制了电子烟气溶胶诱导的促炎MQ极化，并恢复了MQ的吞噬活性。电子烟暴露改变肺脂质稳态，从而通过诱导M1型MQ引发炎症并损害吞噬功能，这可能是电子烟在健康状态下诱导肺部炎症以及在疾病状态下导致炎症加重的一个潜在原因。
