β-carotene alleviates LPS-induced inflammation through regulating STIM1/ORAI1 expression in bovine mammary epithelial cells

Abstract

β-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 β-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-κB signaling. However, overexpression of STIM1 or ORAI1 induced inflammatory response by activating NF-κB signaling pathway, and which had synergistic effect with LPS. β-carotene inhibited NF-κB activation by decreasing STIM1/ORAI1 expression, and thus alleviated LPS-induced inflammation in BMECs. Therefore, SOCE-targeting inhibitors are promising as new anti-inflammatory agents, and β-carotene may be considered for the prevention of mastitis in dairy cows.

Keywords: BMECs; Ca(2+); LPS; NF-κB; STIM1/ORAI1; β-carotene.