Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells.
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells.
复制标题
DOI：
10.3390/ijms23137130
复制
发表时间：
2022-06-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
促炎因子如肿瘤坏死因子-α (TNF-α)通过激活核因子κB （NF-κB）信号通路诱导细胞内粘附分子-1 （ICAM-1）的表达。在本研究中，我们发现葫芦素B在TNF-α或白细胞介素-1α刺激下可降低人肺腺癌A549细胞中ICAM-1的表达。我们进一步研究了葫芦素B下调TNF-α-诱导的ICAM-1表达的机制。葫芦素B抑制TNF-α刺激的A549细胞中NF-κB亚基RelA的核易位和i -κB α的磷酸化。葫芦素B选择性下调TNF受体1 （TNF- r1）的表达，而不影响三种衔接蛋白（即TRADD、RIPK1和TRAF2）。TNF-α-转换酶抑制剂可抑制葫芦素B对TNF- r1表达的下调。谷胱甘肽、n-乙酰- l-半胱氨酸可在较小程度上减弱葫芦素B对TNF-α-诱导的ICAM-1表达的抑制作用，提示α、β-不饱和羰基片段对抗炎活性至关重要。本研究结果表明，葫芦素B在TNF-α-依赖的NF-κB信号通路的初始阶段下调TNF- r1的表达。
Pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), induce the expression of intracellular adhesion molecule-1 (ICAM-1) by activating the nuclear factor κB (NF-κB) signaling pathway. In the present study, we found that cucurbitacin B decreased the expression of ICAM-1 in human lung adenocarcinoma A549 cells stimulated with TNF-α or interleukin-1α. We further investigated the mechanisms by which cucurbitacin B down-regulates TNF-α-induced ICAM-1 expression. Cucurbitacin B inhibited the nuclear translocation of the NF-κB subunit RelA and the phosphorylation of IκBα in A549 cells stimulated with TNF-α. Cucurbitacin B selectively down-regulated the expression of TNF receptor 1 (TNF-R1) without affecting three adaptor proteins (i.e., TRADD, RIPK1, and TRAF2). The TNF-α-converting enzyme inhibitor suppressed the down-regulation of TNF-R1 expression by cucurbitacin B. Glutathione, N-acetyl-L-cysteine, and, to a lesser extent, L-cysteine attenuated the inhibitory effects of cucurbitacin B on the TNF-α-induced expression of ICAM-1, suggesting that an α,β-unsaturated carbonyl moiety is essential for anti-inflammatory activity. The present results revealed that cucurbitacin B down-regulated the expression of TNF-R1 at the initial step in the TNF-α-dependent NF-κB signaling pathway.
登录
查看更多内容
影响因子：
5.5
作者：
Yokomichi T;Morimoto K;Oshima N;Yamada Y;Fu L;Taketani S;Ando M;Kataoka T
通讯作者：
Kataoka T
影响因子：
4
作者：
Jin, Hong Ri;Jin, Xuejun;Lee, Jung Joon
通讯作者：
Lee, Jung Joon
影响因子：
0.7
作者：
Ku, Jin Mo;Hong, Se Hyang;Ko, Seong-Gyu
通讯作者：
Ko, Seong-Gyu
影响因子：
7.9
作者：
Ku, Jin Mo;Hong, Se Hyang;Ko, Seong-Gyu
通讯作者：
Ko, Seong-Gyu
影响因子：
5.1
作者：
Dat, Nguyen Tien;Jin, Xuejun;Lee, Jung Joon
通讯作者：
Lee, Jung Joon