a School BioSciences and Technology , Vellore Institute of Technology, VIT University , Vellore , India.
b Department of Chemical Pathology , Universiti Sains Malaysia , Kubang Kerian , Malaysia.
Immunol Invest. 2019 Jul;48(5):451-465. doi: 10.1080/08820139.2019.1566355. Epub 2019 Jan 28.
Lipopolysaccharide (LPS) induces apoptosis in murine macrophages through the autocrine secretion of tumor necrosis factor (TNF)-α and nitric oxide (NO). LPS-induced inflammation in murine macrophages is associated with hydrogen sulfide (HS) production. In this present study, we reported the novel role of HS in LPS-induced apoptosis and its underlying molecular mechanism specifically at late phases in murine macrophage cells. Stimulation of RAW 264.7 macrophages with LPS resulted in a time- and dose-dependent induction of apoptosis. We observed that the LPS-induced early apoptosis (associated with TNF-α secretion) in macrophages was not inhibited in the presence of HS inhibitor (DL-propargylglycine), whereas early apoptosis was absent in the presence of TNF receptor antibody. Interestingly, LPS-induced late apoptosis paralleled with HS production was reduced in the presence of HS inhibitor but not with TNF receptor antibody. The late apoptotic events mediated by HS and not the TNF-α induced early apoptosis correlated significantly with the induction of p53 and Bax expression in LPS-induced macrophages. Thus, it is possible that RAW 264.7 murine macrophages treated with LPS mediated early apoptosis through TNF-α and the late apoptotic events through the production of HS.
脂多糖（LPS）通过自分泌肿瘤坏死因子（TNF）-α和一氧化氮（NO）诱导小鼠巨噬细胞凋亡。LPS 诱导的小鼠巨噬细胞炎症与硫化氢（HS）的产生有关。在本研究中，我们报道了 HS 在 LPS 诱导的凋亡中的新作用及其在小鼠巨噬细胞晚期阶段的潜在分子机制。用 LPS 刺激 RAW 264.7 巨噬细胞导致凋亡的时间和剂量依赖性诱导。我们观察到，在 HS 抑制剂（DL-丙炔甘氨酸）存在的情况下，LPS 诱导的巨噬细胞早期凋亡（与 TNF-α分泌有关）并未被抑制，而在 TNF 受体抗体存在的情况下早期凋亡不存在。有趣的是，LPS 诱导的与 HS 产生平行的晚期凋亡在 HS 抑制剂存在的情况下减少，但在 TNF 受体抗体存在的情况下不减少。HS 介导的晚期凋亡事件而不是 TNF-α诱导的早期凋亡与 LPS 诱导的巨噬细胞中 p53 和 Bax 表达的诱导显著相关。因此，LPS 处理的 RAW 264.7 小鼠巨噬细胞可能通过 TNF-α介导早期凋亡，通过 HS 的产生介导晚期凋亡事件。
