Yoou Myoung-Schook, Yoon Kyoung Wan, Choi Youngjin, Kim Hyung-Min, Jeong Hyun-Ja
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Department of Biotechnology, Hoseo University, 20, Hoseo-ro 79beon-gil, Baebang-eup, Asan, Chungcheongnam-do 31499, Republic of Korea.
Eur J Pharmacol. 2017 May 5;802:1-6. doi: 10.1016/j.ejphar.2017.02.033. Epub 2017 Feb 20.
Atopic dermatitis (AD) is known to aggravate by thymic stromal lymphopoietin (TSLP) and TSLP is also known to up-regulate mast cell proliferation via production of interleukin (IL)-13. Thus, we investigated whether cordycepin could regulate mast cell proliferation induced by TSLP in human mast cell line, HMC-1 cell. Cordycepin significantly diminished the production and mRNA of IL-13 through the down-regulation of phosphorylated-signal transducer and activation of transcription 6 in the TSLP-stimulated HMC-1 cells. Cordycepin also significantly diminished the cell proliferation via down-regulating MDM2 and Bcl2 levels and up-regulating p53, caspase-3, and cleaved poly ADP-ribose polymerase levels in the TSLP-stimulated HMC-1 cells. Moreover, cordycepin significantly diminished the production of IL-6, tumor necrosis factor-α, and IL-1β in the TSLP-stimulated HMC-1 cells. In conclusion, our study shows that cordycepin has potential effect for the treatment of allergic inflammatory diseases through the blockade of IL-13 and MDM2 exacerbated by TSLP.
已知特应性皮炎(AD)会因胸腺基质淋巴细胞生成素(TSLP)而加重,并且已知TSLP会通过产生白细胞介素(IL)-13来上调肥大细胞增殖。因此,我们研究了虫草素是否能调节人肥大细胞系HMC-1细胞中由TSLP诱导的肥大细胞增殖。虫草素通过下调TSLP刺激的HMC-1细胞中磷酸化信号转导子和转录激活因子6,显著减少了IL-13的产生和mRNA水平。虫草素还通过下调TSLP刺激的HMC-1细胞中的MDM2和Bcl2水平,并上调p53、半胱天冬酶-3和裂解的聚ADP-核糖聚合酶水平,显著减少了细胞增殖。此外,虫草素显著减少了TSLP刺激的HMC-1细胞中IL-6、肿瘤坏死因子-α和IL-1β的产生。总之,我们的研究表明,虫草素通过阻断由TSLP加剧的IL-13和MDM2,对过敏性炎症疾病具有潜在的治疗作用。