title: TNF binding protein of variola virus acts as a TNF antagonist at epicutaneous application.
abstract: 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.
authors.forename: Irina P
authors.initials: IP
authors.lastname: Gileva
authors.forename: Elena A
authors.initials: EA
authors.lastname: Viazovaia
authors.forename: Ludmila B
authors.initials: LB
authors.lastname: Toporkova
authors.forename: Dondok D
authors.initials: DD
authors.lastname: Tsyrendorzhiev
authors.forename: Sergei N
authors.initials: SN
authors.lastname: Shchelkunov
authors.affiliation: FSBI Research Institute of Clinical Immunology RAMS SB, 14, Jadrintsevskaya street, Novosibirsk, 630099, Russia. irorl@mail.ru.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Orlovskaya
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008807:Mice, Inbred BALB C; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology; D012901:Variola virus; D014764:Viral Proteins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C089458:crmB protein, Orthopoxvirus