Hainan University-HSF/LWL Collaborative Innovation Laboratory, School of Food Science and Engineering, Hainan University, Haikou, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China.
Hunan Kouweiwang Group Co., Ltd, Hunan 413499, China.
Int J Biol Macromol. 2024 Apr;263(Pt 1):130076. doi: 10.1016/j.ijbiomac.2024.130076. Epub 2024 Feb 13.
The elucidation of the immunomodulatory molecular mechanisms of polysaccharides has contributed to their further development and application. In this study, the effect of Areca inflorescence polysaccharide (AFP2a) on macrophage activation was confirmed and the detailed mechanisms were investigated based on a comprehensive transcriptional study and specific inhibitors. The results showed that AFP2a induced macrophage activation (M1 polarization), promoting macrophage proliferation, reactive oxygen species production, nitric oxide and cytokine release, and costimulatory molecule expression. RNA-seq analysis identified 5919 differentially expressed genes (DEGs). For DEGs, GO, KEGG, and Reactome enrichment analyses and PPI networks were conducted, elucidating that AFP2a activated macrophages mainly by triggering the Toll-like receptor cascade and corresponding adapter proteins (TIRAP and TRIF), thereby resulting in downstream NF-κB, TNF, and JAK-STAT signaling pathway expression. The inhibition assay revealed that TLR4 and TLR2 were essential for the recognition of AFP2a. This work provides an in-depth understanding of the immunoregulatory mechanism of AFP2a while offering a molecular basis for AFP2a to serve as a potential natural immunomodulator.
阐明多糖的免疫调节分子机制有助于它们的进一步发展和应用。在这项研究中，基于全面的转录组研究和特定的抑制剂，证实了荖花多糖（AFP2a）对巨噬细胞激活的作用，并研究了其详细机制。结果表明，AFP2a 诱导巨噬细胞活化（M1 极化），促进巨噬细胞增殖、活性氧物质产生、一氧化氮和细胞因子释放以及共刺激分子表达。RNA-seq 分析鉴定出 5919 个差异表达基因（DEGs）。对 DEGs 进行 GO、KEGG 和 Reactome 富集分析和 PPI 网络分析，阐明 AFP2a 主要通过触发 Toll 样受体级联和相应的衔接蛋白（TIRAP 和 TRIF）激活巨噬细胞，从而导致下游 NF-κB、TNF 和 JAK-STAT 信号通路表达。抑制试验表明 TLR4 和 TLR2 是 AFP2a 识别所必需的。这项工作深入了解了 AFP2a 的免疫调节机制，为 AFP2a 作为一种潜在的天然免疫调节剂提供了分子基础。
