Gileva Irina P, Viazovaia Elena A, Toporkova Ludmila B, Tsyrendorzhiev Dondok D, Shchelkunov Sergei N, Orlovskaya Irina A
FSBI Research Institute of Clinical Immunology RAMS SB, 14, Jadrintsevskaya street, Novosibirsk, 630099, Russia.
Curr Pharm Biotechnol. 2015;16(1):72-6. doi: 10.2174/1389201015666141126114945.
VARV-CrmB is a TNF binding protein of variola virus. VARV-CrmB protein was previously shown to be active as a TNF-antagonist in a number of in vivo and in vitro models. Here we investigated the epicutaneous effect of recombinant VARV-CrmB protein using an experimental model of muTNFinduced migration of skin leukocytes as well as colony forming activity of bone marrow cells (BMC). Epiсutaneous applications of muTNF enhanced the number of cells migrating from skin flaps of BALB/c mice, whereas subsequent applications of VARV-CrmB protein in 30 min after muTNF, abolished that effect. Epicutaneously applied muTNF influenced the activity of committed hematopoietic progenitors causing a reduction of erythroid (BFUe+CFUe) colonies and increase of granulocyte-macrophage (CFU-GM) colonies in the colony-forming tests. VARV-CrmB, applied in combination with muTNF, demonstrated an ability to reverse this effect, namely, to increase BFUe+CFUe and reduce CFU-GM back to the control levels. Taking together, these data demonstrate the TNF-blocking properties of VARV-CrmB in vivo at epicutaneous applications. As effective TNF antagonist VARV-CrmB protein might be conceded as a beneficial candidate for future research and development of therapeutic approaches in the field of inflammatory skin diseases.
天花病毒CrmB蛋白（VARV-CrmB）是天花病毒的一种肿瘤坏死因子（TNF）结合蛋白。先前研究表明，在许多体内和体外模型中，VARV-CrmB蛋白作为TNF拮抗剂具有活性。在此，我们使用小鼠TNF诱导皮肤白细胞迁移以及骨髓细胞（BMC）集落形成活性的实验模型，研究了重组VARV-CrmB蛋白的表皮效应。表皮应用小鼠TNF可增加BALB/c小鼠皮瓣迁移的细胞数量，而在应用小鼠TNF 30分钟后随后应用VARV-CrmB蛋白，则可消除该效应。表皮应用小鼠TNF影响定向造血祖细胞的活性，导致集落形成试验中红系（BFUe+CFUe）集落减少，粒细胞-巨噬细胞（CFU-GM）集落增加。与小鼠TNF联合应用的VARV-CrmB表现出逆转这种效应的能力，即增加BFUe+CFUe并将CFU-GM降低至对照水平。综上所述，这些数据证明了表皮应用时VARV-CrmB在体内具有TNF阻断特性。作为一种有效的TNF拮抗剂，VARV-CrmB蛋白可能被认为是未来炎症性皮肤病治疗方法研发的有益候选物。
