Danilkovich Alexey V, Turobov Valery I, Palikov Victor A, Palikova Yulia A, Shepelyakovskaya Anna O, Mikhaylov Evgeniy S, Slashcheva Gulsara A, Shadrina Tatiana E, Shaykhutdinova Elvira R, Rasskazova Ekaterina A, Tukhovskaya Elena A, Khokhlova Oksana N, Dyachenko Igor A, Ismailova Alina M, Zinchenko Dmitry V, Navolotskaya Elena V, Lipkin Valery M, Murashev Arkady N, Udovichenko Igor P
State Center for Sciences by Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, 142290 Pushchino, Russia.
Fundamental Biotechnology Department, RosBioTech University at Pushchino, 3 Prospekt Nauki, 142290 Pushchino, Russia.
Biomedicines. 2023 Oct 21;11(10):2855. doi: 10.3390/biomedicines11102855.
A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure-function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3's ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC = 0.42 μM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague-Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model.
对一种源自小窝蛋白-3结构C端部分的短合成肽进行了测试，以观察其对大鼠实验性自身免疫性脑脊髓炎（EAE）的治疗效果。在新型合成肽pCav3与著名免疫调节剂免疫皮质素之间建立的结构-功能相似性，决定了pCav3在注射pCav3（500 μg/kg）的暗褐鼠（DA）中减轻EAE症状的能力。发现pCav3可干扰从经匀浆注射致敏的DA大鼠淋巴结中提取的淋巴细胞增殖，其IC = 0.42 μM（2.35 μg/mL）。pCav3对EAE的影响与免疫皮质素非常相似。pCav3和免疫皮质素氨基酸序列之间的高度同源性与两种肽在EAE上所显示的治疗活性非常吻合。后一种与pCav3具有同源结构的肽也在EAE上进行了测试，以探究由MHC相关细胞机制所暗示的这些肽之间是否存在结构限制。因此，使用在斯普拉格-道利大鼠中建立的不同自身免疫性疾病模型——胶原诱导性关节炎（CIA），对免疫皮质素进行了进一步研究。建立CIA所使用的遗传平台与EAE有意不同。根据结果得出结论，pCav3和免疫皮质素肽在EAE大鼠模型中的有效性几乎相同，但在类风湿性关节炎大鼠模型中有所不同；因此，疗效可能对用于建立自身免疫性疾病模型的动物的MHC类型敏感。
