Butyrate upregulates the TLR4 expression and the phosphorylation of MAPKs and NK-κB in colon cancer cell in vitro.
Butyrate upregulates the TLR4 expression and the phosphorylation of MAPKs and NK-κB in colon cancer cell in vitro.
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丁酸盐上调结肠癌细胞体外TLR4表达及MAPKs和NK-κB的磷酸化
DOI：
10.3892/ol.2018.9201
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发表时间：
2018-10
期刊：
影响因子：
2.9
通讯作者：
Xia S
中科院分区：
文献类型：
--
作者：
Xiao T;Wu S;Yan C;Zhao C;Jin H;Yan N;Xu J;Wu Y;Li C;Shao Q;Xia S
结直肠粘膜微生物群及其诱导的炎症反应被认为是结直肠癌发生发展的危险因素。以往的研究表明，肠道中共存的微生物群元素，如短链脂肪酸（SCFAs）和脂多糖（LPS），对肠上皮细胞表现出各自的调节作用。不幸的是，丁酸盐和Toll样受体（TLR）信号通路在结肠癌发展中的关系尚未完全阐明。在本研究中，通过体外培养人结肠癌SW 480细胞或小鼠结肠癌CT 26细胞与丁酸和/或TLR 4配体LPS，它被确定为丁酸抑制这些癌细胞的生长和促进凋亡。值得注意的是，TLR 4和CD 14的表达水平显着增加这些丁酸酯处理的细胞，但不是单独的LPS处理的细胞。此外，丁酸盐处理诱导细胞外信号调节激酶、肿瘤蛋白38、c-Jun氨基末端激酶和核因子-κB（NF-κB）p65的磷酸化，进而促进SW 480和CT 26细胞分泌促炎细胞因子肿瘤坏死因子-α，但不促进白细胞介素6的分泌。因此，丁酸盐处理在体外调节TLR 4的表达、丝裂原活化蛋白激酶和NF-κB信号通路活化和促炎反应。虽然确切的机制尚未完全探索，但这些结果表明丁酸和LPS-TLR 4信号传导通过两种不同但相互调节的途径介导结肠癌细胞中的先天免疫。因此，丁酸盐可以通过上调TLR 4表达和活化来进一步启动针对肿瘤细胞的先天免疫，以保持肠内稳态。
Microbiota and its induced inflammation in colorectal mucosa have been considered risk factors for the development of colorectal carcinogenesis. Previous studies demonstrated that the coexisting elements of microbiota in the gut, such as short chain fatty acids (SCFAs) and lipopolysaccharides (LPS), which exhibited regulatory effects on the intestinal epithelial cells individually. Unfortunately, the association between butyrate and the toll-like receptor (TLR) signaling pathway in the development of colon cancer is not fully elucidated. In the present study, by culturing human colon cancer SW480 cells or mouse colon cancer CT26 cells with butyrate and/or TLR4 ligand LPS in vitro, it was identified that butyrate suppressed the growth and promoted apoptosis of these cancer cells. Notably, the expression levels of TLR4 and CD14 were markedly increased on these butyrate-treated cells, but not on LPS-alone treated cells. Additionally, butyrate treatment induced the phosphorylation of extracellular signal-regulated kinase, tumor protein 38, c-Jun NH2-terminal kinase and nuclear factor-κB (NF-κB) p65, and then promoted the pro-inflammatory cytokine tumor necrosis factor-α, but not interleukin 6 secretion in SW480 and CT26 cells. Therefore, butyrate treatment regulates the expression of TLR4, mitogen-activated protein kinase and NF-κB signal pathway activation and pro-inflammatory response in vitro. Although the exact mechanisms have not been fully explored, these results suggested that butyrate and LPS-TLR4 signaling mediated innate immunity in colon cancer cells through two distinct but inter-regulated pathways. Thus, butyrate can further initiate innate immunity against tumor cells by upregulating the TLR4 expression and activation to preserve intestinal homeostasis.
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影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
24.5
作者：
Flemer B;Lynch DB;Brown JM;Jeffery IB;Ryan FJ;Claesson MJ;O'Riordain M;Shanahan F;O'Toole PW
通讯作者：
O'Toole PW
影响因子：
3.8
作者：
Hyzd'alova, M.;Hofmanova, J.;Kozubik, A.
通讯作者：
Kozubik, A.
影响因子：
4.1
作者：
Frosali S;Pagliari D;Gambassi G;Landolfi R;Pandolfi F;Cianci R
通讯作者：
Cianci R
DOI：
10.1158/1078-0432.ccr-13-2483
发表时间：
2014-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bultman SJ
通讯作者：
Bultman SJ