Han Na-Ra, Ko Seong-Gyu, Park Hi-Joon, Moon Phil-Dong
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Antioxidants (Basel). 2023 Feb 8;12(2):417. doi: 10.3390/antiox12020417.
The cytokine oncostatin M (OSM) is regarded as a critical mediator in various inflammatory responses. While the gaseous signaling molecule hydrogen sulfide (HS) plays a role in a variety of pathophysiological conditions, such as hypertension, inflammatory pain, osteoarthritis, ischemic stroke, oxidative stress, retinal degeneration, and inflammatory responses, the underlying mechanism of HS action on OSM expression in neutrophils needs to be clarified. In this work, we studied how HS reduces OSM expression in neutrophil-like differentiated (d)HL-60 cells. To evaluate the effects of HS, sodium hydrosulfide (NaHS, a donor that produces HS), ELISA, real-time PCR (qPCR), immunoblotting, and immunofluorescence staining were utilized. Although exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in upregulated levels of production and mRNA expression of OSM, these upregulated levels were reduced by pretreatment with NaHS in dHL-60 cells. Similarly, the same pretreatment lowered phosphorylated levels of phosphatidylinositol 3-kinase, Akt, and nuclear factor-kB that had been elevated by stimulation with GM-CSF. Overall, our results indicated that HS could be a therapeutic agent for inflammatory disorders via suppression of OSM.
细胞因子抑瘤素M（OSM）被认为是各种炎症反应中的关键介质。虽然气态信号分子硫化氢（HS）在多种病理生理状况中发挥作用，如高血压、炎性疼痛、骨关节炎、缺血性中风、氧化应激、视网膜变性和炎症反应，但HS作用于中性粒细胞中OSM表达的潜在机制仍有待阐明。在这项研究中，我们研究了HS如何降低中性粒细胞样分化的（d）HL-60细胞中OSM的表达。为了评估HS的作用，我们使用了硫化氢供体硫氢化钠（NaHS）、酶联免疫吸附测定（ELISA）、实时定量聚合酶链反应（qPCR）、免疫印迹和免疫荧光染色。尽管暴露于粒细胞巨噬细胞集落刺激因子（GM-CSF）会导致dHL-60细胞中OSM的产生水平和mRNA表达上调，但用NaHS预处理可降低这些上调水平。同样，相同的预处理降低了因GM-CSF刺激而升高的磷脂酰肌醇3激酶、Akt和核因子-κB的磷酸化水平。总体而言，我们的结果表明，HS可能通过抑制OSM成为炎症性疾病的治疗药物。
