Wang Tiantian, Zheng Ruihe, Sun Song
Department of Pharmacy, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Department of Pharmacy, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China; School of Medicine, Xiamen University, Xiamen, Fujian, 361002, China.
Biochem Biophys Res Commun. 2022 Apr 9;599:1-8. doi: 10.1016/j.bbrc.2022.02.015. Epub 2022 Feb 8.
Acute lung injury (ALI) is a significant cause of morbidity and mortality worldwide. To search for a new treatment for acute lung injury, we investigated the effect of escitalopram on lipopolysaccharide (LPS)-induced ALI. Our results showed that escitalopram inhibited salt-inducible kinase 2 (SIK2) activity (IC = 6.36 ± 0.93 μM) and triggered histone deacetylase 4 (HDAC4) dephosphorylation. Following its dephosphorylation, HDAC4 translocated into the nucleus, promoted deacetylation and cytoplasmic shuttling of p65, thus inhibited LPS-induced pro-inflammatory cytokine production. Moreover, escitalopram markedly ameliorated the inflammatory responses, reduced neutrophils infiltration and attenuated LPS-induced pulmonary injury in mice. Taken together, we identified a previously unexplored role for escitalopram in SIK2/HDAC4/NF-κB pathway, therefore escitalopram may be considered as a new treatment for ALI.
急性肺损伤（ALI）是全球范围内发病和死亡的重要原因。为了寻找急性肺损伤的新治疗方法，我们研究了艾司西酞普兰对脂多糖（LPS）诱导的ALI的影响。我们的结果表明，艾司西酞普兰抑制盐诱导激酶2（SIK2）活性（IC = 6.36 ± 0.93 μM）并引发组蛋白去乙酰化酶4（HDAC4）去磷酸化。去磷酸化后，HDAC4易位至细胞核，促进p65的去乙酰化和细胞质穿梭，从而抑制LPS诱导的促炎细胞因子产生。此外，艾司西酞普兰显著改善了炎症反应，减少了中性粒细胞浸润，并减轻了LPS诱导的小鼠肺损伤。综上所述，我们确定了艾司西酞普兰在SIK2/HDAC4/NF-κB通路中以前未被探索的作用，因此艾司西酞普兰可被视为ALI的一种新治疗方法。
