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트롬복산 수용체 활성화가 인터루킨-8 발현에 미치는 영향
전화진(Hwa-Jin Jeon),김수륜(Su-Ryun Kim),박현주(Hyun-Joo Park),김미경(Mi-Kyoung Kim),김도원(Do-Won Kim),배수경(Soo-Kyung Bae),배문경(Moon-Kyoung Bae) 한국생물공학회 2013 KSBB Journal Vol.28 No.1
Thromboxane A₂ (TXA₂) is one of major proinflammatory mediators, plays an important role in the development of vascular inflammatory diseases. TXA₂ acting through the thromboxane receptor regulates multiple pathways and genes in a variety of cells. In this study, we report that the activation of thromboxane receptor with U46619 increases the interleukin-8 (IL-8) mRNA in vascular endothelial cells. We also demonstrated that U46619 produces the activations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK), which is required for endothelial IL-8 production. And U46619 enhanced mRNA stability of IL-8 transcripts in endothelial cells. Moreover, inhibition of ERK1/2 or p38MAPK reduced monocyte adhesion to aortic endothelium stimulated by U46619. Therefore, these results suggest that activation of thromboxane receptor promotes the expression of IL-8 via ERK1/2 and p38MAPK activation in endothelial cells.
박선영(Seon-Yeong Park),강용규(Yong-Gyu Kang),배윤희(Yun-Hee Bae),김수륜(Su-Ryun Kim),박현주(Hyun-Joo Park),강영순(Young-Soon Kang),김미경(Mi-Kyoung Kim),위희준(Hee-Jun Wee),장혜옥(Hye-Ock Jang),배문경(Moon-Kyoung Bae),우재석(Jae Suk 한국생물공학회 2013 KSBB Journal Vol.28 No.1
Curcumin has diverse anticancer activities that lead to tumor growth inhibition of cancer cells and induction of apoptosis. Curcumin is involved in the regulation of multiple genes via transcription factors including NF-kB, STATs, AP1, and SP. Notch signaling plays critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thereby may contribute to the development of various cancers involving breast cancer. This study was to investigate the effects of curcumin on Notch1 gene expression and to explore the underlying mechanism. Here, we found that curcumin decreased the levels of Notch1 mRNA and protein in MDA-MB-231 human breast cancer cells, along with the downregulation of Sp family genes (Sp1, Sp2, Sp3, and Sp4). The repressive effect of curcumin on Notch1 gene transcription was confirmed by performing Notch1 promoter- driven reporter assay and three Sp-binding sites were identified on Notch1 promoter that may act as curcumin-respose elements. Moreover, treatment with mitramycin A, a specific Sp inhibitor, decreased the levels of Notch1 mRNA and protein in human breast cancer cells. Taken together, our results indicate that Notch1 gene expression is downregulated by curcumin, at least in part, through the suppression of Sp family, which may lead to apoptosis in human breast cancer cells.