College of Pharmacy and Medical Research Center (CICT), Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Food Chem Toxicol. 2012 Sep;50(9):3190-7. doi: 10.1016/j.fct.2012.05.051. Epub 2012 Jun 8.
Paecilomyces cicadae have been reported to have immunomodulatory properties. In this study, we investigated the effect of polysaccharide (PCP) isolated from P. cicadae on the macrophages. PCP increased the production of nitric oxide (NO) and the gene expression of IL-1β, IL-6, and TNF-α in RAW 264.7 cells. To investigate the membrane receptor, we examined the effect of PCP on primary macrophages isolated from wild type C3H/HeN and C3H/HeJ mice having mutant-TLR4. PCP induced NO production and cytokine gene expression in macrophages from C3H/HeN, but not from tlr4-mutated C3H/HeJ mice, which suggests that TLR4 is the membrane receptor for PCP. PCP induced the phosphorylation of ERK, JNK, and p38, and the nuclear translocation of NF-κB p50/p65, which are the main signaling molecules downstream from TLR4. Among them, p38 and NF-κB signaling played a crucial role in PCP-induced NO production by macrophages. These results indicate that PCP activates macrophages through the TLR4 signaling pathway.
蝉拟青霉已被报道具有免疫调节特性。在本研究中，我们研究了蝉拟青霉多糖（PCP）对巨噬细胞的作用。PCP 增加了 RAW 264.7 细胞中一氧化氮（NO）的产生和 IL-1β、IL-6 和 TNF-α 的基因表达。为了研究细胞膜受体，我们检测了 PCP 对来自野生型 C3H/HeN 和具有突变型 TLR4 的 C3H/HeJ 小鼠的原代巨噬细胞的影响。PCP 诱导了来自 C3H/HeN 的巨噬细胞中 NO 的产生和细胞因子基因的表达，但不能诱导来自 TLR4 突变型 C3H/HeJ 小鼠的巨噬细胞中 NO 的产生，这表明 TLR4 是 PCP 的细胞膜受体。PCP 诱导了 ERK、JNK 和 p38 的磷酸化，以及 NF-κB p50/p65 的核易位，这些都是 TLR4 下游的主要信号分子。其中，p38 和 NF-κB 信号通路在 PCP 诱导的巨噬细胞 NO 产生中起着至关重要的作用。这些结果表明 PCP 通过 TLR4 信号通路激活巨噬细胞。
