Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Department of Psychiatry, Faculty of Medicine and Health Sciences, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
Peptides. 2018 Mar;101:150-156. doi: 10.1016/j.peptides.2018.01.013. Epub 2018 Feb 3.
Quorum sensing peptides (QSP) are an important class of bacterial peptides which can have an effect on human host cells. These peptides are used by bacteria to communicate with each other. Some QSP are able to cross the blood-brain barrier and reach the brain parenchyma. However, nothing is known about the effects of these peptides in the brain. Therefore, 85 quorum sensing peptides were screened on six different neuronal cell lines using MTT toxicity, neurite differentiation, cytokine production and morphology as biological outcomes. This primary screening resulted in 22 peptides with effects observed on neuronal cell lines, indicating a possible role in the gut-brain axis. Four peptides (Q138, Q143, Q180 and Q212) showed induction of neurite outgrowth while two peptides (Q162 and Q208) inhibited NGF-induced neurite outgrowth in PC12 cells. Eight peptides (Q25, Q135, Q137, Q146, Q151, Q165, Q208 and Q298) induced neurite outgrowth in human SH-SY5Y neuroblastoma cells. Two peptides (Q13 and Q52) were toxic for SH-SY5Y cells and one (Q123) for BV-2 microglia cells based on the MTT assay. Six peptides had an effect on BV-2 microglia, Q180, Q184 and Q191 were able to induce IL-6 expression and Q164, Q192 and Q208 induced NO production. Finally, Q75 and Q147 treated C8D1A astrocytes demonstrated a higher fraction of round cells. Overall, these in vitro screening study results indicate for the first time possible effects of QSP on neuronal cells.
群体感应肽 (QSP) 是一类重要的细菌肽，可对人类宿主细胞产生影响。这些肽被细菌用来相互交流。一些 QSP 能够穿过血脑屏障并到达脑实质。然而，目前尚不清楚这些肽在大脑中的作用。因此，使用 MTT 毒性、神经突分化、细胞因子产生和形态学作为生物学终点，在六种不同的神经元细胞系上筛选了 85 种群体感应肽。这种初步筛选导致 22 种肽对神经元细胞系有作用，表明它们在肠脑轴中可能具有作用。四种肽 (Q138、Q143、Q180 和 Q212) 显示出诱导神经突生长的作用，而两种肽 (Q162 和 Q208) 抑制 PC12 细胞中 NGF 诱导的神经突生长。八种肽 (Q25、Q135、Q137、Q146、Q151、Q165、Q208 和 Q298) 诱导人 SH-SY5Y 神经母细胞瘤细胞的神经突生长。两种肽 (Q13 和 Q52) 基于 MTT 测定对 SH-SY5Y 细胞有毒，一种肽 (Q123) 对 BV-2 小胶质细胞有毒。六种肽对 BV-2 小胶质细胞有作用，Q180、Q184 和 Q191 能够诱导 IL-6 表达，Q164、Q192 和 Q208 诱导 NO 产生。最后，用 Q75 和 Q147 处理的 C8D1A 星形胶质细胞显示出更高比例的圆形细胞。总的来说，这些体外筛选研究结果首次表明 QSP 对神经元细胞可能具有作用。
