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硫化氢可降低活化肥大细胞中胸腺基质淋巴细胞生成素的水平。

Hydrogen sulfide diminishes the levels of thymic stromal lymphopoietin in activated mast cells.

作者信息

Han Na-Ra, Moon Phil-Dong, Jeong Hyun-Ja, Kim Hyung-Min

机构信息

Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.

Department of Food Technology and Biochip Research Center, Hoseo University, 165, Sechul-ri, Asan, Chungnam, 336-795, Republic of Korea.

出版信息

Arch Dermatol Res. 2016 Mar;308(2):103-13. doi: 10.1007/s00403-016-1619-x. Epub 2016 Jan 20.

Abstract

Bamboo salt (BS) is a Korean traditional type of salt and has been reported to have therapeutic effects on allergic inflammation. Thymic stromal lymphopoietin (TSLP) aggravates inflammation in the pathogenesis of allergic reactions, such as allergic rhinitis (AR). To confirm an active compound of BS, we investigated the effect of sulfur, a compound of BS, on the levels of TSLP in a human mast cell line, HMC-1 cells and a mouse model of AR using hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaSH). We treated NaSH or BS in HMC-1 cells and activated the HMC-1 cells with phorbol myristate acetate and calcium ionophore A23187 (PMACI). ELISA for the production measurement of TSLP, PCR for the mRNA expression measurement of TSLP, and western blot analysis for the expression measurement of upstream mediators were performed. Mice were treated with NaSH and sensitized with ovalbumin (OVA). The levels of TSLP were measured in serum and nasal mucosa tissue in an OVA-induced AR mouse model. NaSH or BS diminished the production and mRNA expression of TSLP as well as interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the PMACI-activated HMC-1 cells. NaSH or BS diminished the level of intracellular calcium in the PMACI-activated HMC-1 cells. NaSH or BS reduced the expression and activity of caspase-1 in the PMACI-activated HMC-1 cells. And NaSH or BS inhibited the expression of receptor interacting protein-2 and the phosphorylation of extracellular signal-regulated kinase in the PMACI-activated HMC-1 cells. The translocation of NF-κB into the nucleus as well as the phosphorylation and degradation of IκBα in the cytoplasm were diminished by NaSH or BS in the PMACI-activated HMC-1 cells. Furthermore, NaSH inhibited the production of TSLP, IL-6, and IL-8 in TNF-α-activated HMC-1 cells. Finally, the administration of NaSH showed a decrease in number of rubs on mice with OVA-induced AR. And the levels of immunoglobulin E and TSLP in the serum and the level of TSLP in the nasal mucosa tissue of the OVA-induced AR mice were reduced by NaSH. In conclusion, these findings show that H2S, as an active compound of BS is a potential agent to cure allergic inflammation.

摘要

竹盐是一种韩国传统盐类,据报道对过敏性炎症具有治疗作用。胸腺基质淋巴细胞生成素(TSLP)在过敏性反应(如过敏性鼻炎,AR)的发病机制中会加剧炎症。为了确定竹盐的活性成分,我们使用硫化氢(H₂S)供体硫氢化钠(NaSH),研究了竹盐的一种成分硫对人肥大细胞系HMC-1细胞以及AR小鼠模型中TSLP水平的影响。我们在HMC-1细胞中处理NaSH或竹盐,并用佛波酯肉豆蔻酸酯乙酸盐和钙离子载体A23187(PMACI)激活HMC-1细胞。进行酶联免疫吸附测定(ELISA)以测量TSLP的产生,进行聚合酶链反应(PCR)以测量TSLP的mRNA表达,并进行蛋白质免疫印迹分析以测量上游介质的表达。用NaSH处理小鼠并用卵清蛋白(OVA)致敏。在OVA诱导的AR小鼠模型中测量血清和鼻黏膜组织中TSLP的水平。NaSH或竹盐减少了PMACI激活的HMC-1细胞中TSLP以及白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α的产生和mRNA表达。NaSH或竹盐降低了PMACI激活的HMC-1细胞中的细胞内钙水平。NaSH或竹盐降低了PMACI激活的HMC-1细胞中半胱天冬酶-1的表达和活性。并且NaSH或竹盐抑制了PMACI激活的HMC-1细胞中受体相互作用蛋白-2的表达和细胞外信号调节激酶的磷酸化。在PMACI激活的HMC-1细胞中,NaSH或竹盐减少了NF-κB向细胞核的转位以及细胞质中IκBα的磷酸化和降解。此外,NaSH抑制了TNF-α激活的HMC-1细胞中TSLP、IL-6和IL-8的产生。最后,给予NaSH使OVA诱导的AR小鼠的抓挠次数减少。NaSH降低了OVA诱导的AR小鼠血清中的免疫球蛋白E和TSLP水平以及鼻黏膜组织中的TSLP水平。总之,这些发现表明,作为竹盐活性成分的H₂S是治疗过敏性炎症的潜在药物。

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