β-carotene alleviates LPS-induced inflammation through regulating STIM1/ORAI1 expression in bovine mammary epithelial cells
β-carotene alleviates LPS-induced inflammation through regulating STIM1/ORAI1 expression in bovine mammary epithelial cells
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DOI：
10.1016/j.intimp.2022.109377
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发表时间：
2022-11-02
影响因子：
5.6
通讯作者：
Shen, Xiangzhen
中科院分区：
文献类型：
--
作者：
Meng, Meijuan;Huo, Ran;Shen, Xiangzhen
-胡萝卜素具有抗炎特性。STIM1(Stromol相互作用分子1)/ORAI1 （Orai calcium release-activated calcium modulator 1）是一种重要的炎症受体，参与炎症对细胞内钙信号的调节。本研究的目的是阐明STIM1/ orai1介导的Ca2+信号与炎症的相关性，以及0-胡萝卜素对脂多糖（LPS）诱导的牛乳腺上皮细胞（BMECs）的抗炎作用。结果表明，LPS通过上调STIM1和ORAI1的表达激活SOCE通道，诱导Ca2+内流，导致细胞损伤。STO-609、BTP2、STIM1或ORAI1通过抑制NF-cB信号传导来减弱lps诱导的炎症。而STIM1或ORAI1过表达通过激活NF-cB信号通路诱导炎症反应，并与LPS有协同作用。0-胡萝卜素通过降低STIM1/ORAI1表达抑制NF-cB活化，从而减轻脂多糖诱导的bmec炎症。因此，sosotarget抑制剂是一种很有前景的新型抗炎药物，0-胡萝卜素可能被考虑用于奶牛乳腺炎的预防。
beta-carotene has anti-inflammatory properties. STIM1(Stromol interaction molecule 1)/ORAI1 (Orai calcium release-activated calcium modulator 1) is an important inflammatory receptor, participating in the regulation of intracellular calcium signals by inflammation. The aim of this study was to clarify the correlation between STIM1/ORAI1-mediated Ca2+ signaling and inflammation and the anti-inflammatory effect of 0-carotene on lipopolysaccharide (LPS)-induced bovine mammary epithelial cells (BMECs). The results showed that LPS activated SOCE channels and induced Ca2+ influx via up-regulating the expression of STIM1 and ORAI1, leading to cell injury. STO-609, BTP2, STIM1 or ORAI1 sclienced attenuated LPS-induced inflammation by inhibiting NF-cB signaling. However, overexpression of STIM1 or ORAI1 induced inflammatory response by activating NF-cB signaling pathway, and which had synergistic effect with LPS. 0-carotene inhibited NF-cB activation by decreasing STIM1/ORAI1 expression, and thus alleviated LPS-induced inflammation in BMECs. Therefore, SOCEtargeting inhibitors are promising as new anti-inflammatory agents, and 0-carotene may be considered for the prevention of mastitis in dairy cows.