Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
Int J Mol Sci. 2022 Jan 27;23(3):1440. doi: 10.3390/ijms23031440.
The blue-green alga is rich in phycocyanins, that exhibit a wide range of pharmacological actions. C-phycocyanin (C-PC), in particular, possesses hepatoprotective, nephroprotective, antioxidant, and anticancer effects. Furthermore, several studies have reported both anti- and proinflammatory properties of this pigment. However, the precise mechanism(s) of action of C-PC in these processes remain largely unknown. Therefore, here we explored the C-PC effect in in vitro microglia activation. The effect of C-PC on the expression and release of IL-1β and TNF-α and the activation of NF-κB was examined in primary microglia by real-time PCR, ELISA, and immunofluorescence. Treatment with C-PC up-regulated the expression and release of IL-1β and TNF-α. C-PC also promoted the nuclear translocation of the NF-κB transcription factor. Then, to elucidate the molecular mechanisms for the immunoregulatory function of C-PC, we focused on investigating the role of Toll-like receptor 4 (TLR4). Accordingly, several TLR4 inhibitors have been used. Curcumin, ciprofloxacin, L48H37, and CLI-095 that suppresses specifically TLR4 signaling, blocked IL-1β and TNF-α. Overall, these results indicate the immunomodulatory effect of C-PC in microglia cultures and show for the first time that the molecular mechanism implicated in this effect may involve TLR4 activation.
蓝绿藻富含藻蓝蛋白，具有广泛的药理作用。特别是 C-藻蓝蛋白（C-PC）具有保肝、护肾、抗氧化和抗癌作用。此外，多项研究报道了这种色素的抗炎和促炎特性。然而，C-PC 在这些过程中的确切作用机制仍知之甚少。因此，我们在这里探讨了 C-PC 在体外小胶质细胞激活中的作用。通过实时 PCR、ELISA 和免疫荧光法研究了 C-PC 对原代小胶质细胞中 IL-1β和 TNF-α的表达和释放以及 NF-κB 激活的影响。C-PC 处理可上调 IL-1β和 TNF-α的表达和释放。C-PC 还促进了 NF-κB 转录因子的核转位。然后，为了阐明 C-PC 免疫调节功能的分子机制，我们专注于研究 Toll 样受体 4（TLR4）的作用。因此，使用了几种 TLR4 抑制剂。姜黄素、环丙沙星、专门抑制 TLR4 信号的 L48H37 和 CLI-095 阻断了 IL-1β和 TNF-α。总的来说，这些结果表明 C-PC 在小胶质细胞培养物中具有免疫调节作用，并首次表明涉及这种作用的分子机制可能涉及 TLR4 激活。
