Department of Marine Bio Food Science, Gangneung-Wonju National University, Gangneung 25457, Gangwon, Republic of Korea.
Department of Agricultural Science, Faculty of Agriculture Natural Resources and Environment, Naresuan University, Phitsanulok 65000, Thailand.
Int J Mol Sci. 2024 Oct 3;25(19):10660. doi: 10.3390/ijms251910660.
In this study, a mixture of , , , and (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E (PGE) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of . PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages.
在这项研究中,研究了 、 、 和 (PPCRE)混合物对 RAW264.7 细胞的免疫增强作用及其分子机制。PPCRE 显著增加了一氧化氮(NO)和前列腺素 E(PGE)的产生,这取决于浓度,同时没有细胞毒性。PPCRE 明显上调了免疫相关细胞毒性因子的 mRNA 和蛋白质表达,如环加氧酶(COX)-1、COX-2 和诱导型一氧化氮合酶(iNOS)以及促炎细胞因子,如白细胞介素(IL)-1β、IL-6 和肿瘤坏死因子α(TNF-α),以及 的 mRNA 水平。PPCRE 通过上调细胞外信号调节激酶(ERK)、应激激活蛋白激酶/Jun N-末端激酶(SAPK/JNK)和 p38 的磷酸化,增加丝裂原激活蛋白激酶(MAPK)信号通路。此外,PPCRE 通过增加 NF-κB-p65 的磷酸化,显著激活了核因子 kappa B(NF-κB)信号通路。PPCRE 刺激 RAW264.7 细胞增加了巨噬细胞的吞噬能力。总之,我们的研究发现,PPCRE 通过调节炎症介质和调节巨噬细胞中 MAPK 和 NF-κB 信号通路来改善免疫功能。