Kirikovich Svetlana S, Levites Evgeniy V, Proskurina Anastasia S, Ritter Genrikh S, Dolgova Evgeniya V, Ruzanova Vera S, Oshihmina Sofya G, Snegireva Julia S, Gamaley Svetlana G, Sysoeva Galina M, Danilenko Elena D, Taranov Oleg S, Ostanin Alexandr A, Chernykh Elena R, Kolchanov Nikolay A, Bogachev Sergey S
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Faculty of Biotechnologies, ITMO University, 191002 Saint Petersburg, Russia.
Curr Issues Mol Biol. 2024 Sep 28;46(10):10934-10959. doi: 10.3390/cimb46100650.
Vitamin D transporter (DBP) is a multifunctional protein. Site-specific deglycosylation results in its conversion to group-specific component protein-derived macrophage activating factor (GcMAF), which is capable of activating macrophages. It has been shown that depending on precursor conversion conditions, the resulting GcMAF activates mouse peritoneal macrophages towards synthesis of either pro- (IL-1β, TNF-α-M1 phenotype) or anti-inflammatory (TGF-β, IL-10-M2 phenotype) cytokines. The condition for the transition of the direction of the inflammatory response of macrophages when exposed to GcMAF is the initial glycosylated state of the population of DBP molecules and the associated effective deglycosylation of DBP by β-galactosidase. In vivo experiments with GcMAF exhibiting anti-inflammatory properties on models of induced arthritis in mice and cystitis in rats indicate a significant anti-inflammatory effect of the macrophage activator. The feasibility of unidirectional induction of anti-inflammatory properties of macrophages allows creation of combined therapeutic platforms where M2 macrophages are among the key therapeutic components.
维生素D转运蛋白（DBP）是一种多功能蛋白质。位点特异性去糖基化导致其转化为群体特异性成分蛋白衍生的巨噬细胞激活因子（GcMAF），后者能够激活巨噬细胞。已经表明，根据前体转化条件，产生的GcMAF可激活小鼠腹腔巨噬细胞，使其合成促炎（IL-1β、TNF-α - M1表型）或抗炎（TGF-β、IL-10 - M2表型）细胞因子。巨噬细胞在接触GcMAF时炎症反应方向转变的条件是DBP分子群体的初始糖基化状态以及β-半乳糖苷酶对DBP的相关有效去糖基化。在小鼠诱导性关节炎模型和大鼠膀胱炎模型上进行的具有抗炎特性的GcMAF体内实验表明，巨噬细胞激活剂具有显著的抗炎作用。单向诱导巨噬细胞抗炎特性的可行性使得创建联合治疗平台成为可能，其中M2巨噬细胞是关键治疗成分之一。
