Piekarska Klaudia, Bonowicz Klaudia, Grzanka Alina, Jaworski Łukasz M, Reiter Russel J, Slominski Andrzej T, Steinbrink Kerstin, Kleszczyński Konrad, Gagat Maciej
Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland.
Department of Cell Systems and Anatomy, UT Health, Long School of Medicine, San Antonio, TX 78229, USA.
Metabolites. 2023 Apr 18;13(4):575. doi: 10.3390/metabo13040575.
The immune system, unlike other systems, must be flexible and able to "adapt" to fully cope with lurking dangers. The transition from intracorporeal balance to homeostasis disruption is associated with activation of inflammatory signaling pathways, which causes modulation of the immunology response. Chemotactic cytokines, signaling molecules, and extracellular vesicles act as critical mediators of inflammation and participate in intercellular communication, conditioning the immune system's proper response. Among the well-known cytokines allowing for the development and proper functioning of the immune system by mediating cell survival and cell-death-inducing signaling, the tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) are noteworthy. The high bloodstream concentration of those pleiotropic cytokines can be characterized by anti- and pro-inflammatory activity, considering the powerful anti-inflammatory and anti-oxidative stress capabilities of TGF-β known from the literature. Together with the chemokines, the immune system response is also influenced by biologically active chemicals, such as melatonin. The enhanced cellular communication shows the relationship between the TGF-β signaling pathway and the extracellular vesicles (EVs) secreted under the influence of melatonin. This review outlines the findings on melatonin activity on TGF-β-dependent inflammatory response regulation in cell-to-cell communication leading to secretion of the different EV populations.
与其他系统不同，免疫系统必须具有灵活性，能够“适应”以全面应对潜在危险。从体内平衡到体内平衡破坏的转变与炎症信号通路的激活相关，这会导致免疫反应的调节。趋化细胞因子、信号分子和细胞外囊泡作为炎症的关键介质，参与细胞间通讯，调节免疫系统的正常反应。在通过介导细胞存活和诱导细胞死亡信号来促进免疫系统发育和正常功能的知名细胞因子中，肿瘤坏死因子α（TNF-α）和转化生长因子β（TGF-β）值得关注。考虑到文献中已知的TGF-β强大的抗炎和抗氧化应激能力，这些多效性细胞因子在血液中的高浓度可表现出抗炎和促炎活性。与趋化因子一起，免疫系统反应还受褪黑素等生物活性化学物质的影响。增强的细胞通讯显示了TGF-β信号通路与在褪黑素影响下分泌的细胞外囊泡（EVs）之间的关系。本综述概述了褪黑素在细胞间通讯中对依赖TGF-β的炎症反应调节的活性研究结果，该调节导致不同EV群体的分泌。
