title: Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy.
abstract: Human T-lymphotropic virus type 1 (HTLV-1) induces a strong activation of the immune system, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Physalin F is a secosteroid with potent anti-inflammatory and immunomodulatory activities. The present study aimed to investigate the effects of physalin F on peripheral blood mononuclear cells (PBMC) of HAM/TSP subjects. A concentration-dependent inhibition of spontaneous proliferation of PBMC from HAM/TSP subjects was observed in the presence of physalin F, as evaluated by (3)H-thymidine uptake. The IC50 for physalin F was 0.97 ± 0.11 μM. Flow cytometry analysis using Cytometric Bead Array (CBA) showed that physalin F (10 μM) significantly reduced the levels of IL-2, IL-6, IL-10, TNF-α and IFN-γ, but not IL-17A, in supernatants of PBMC cultures. Next, apoptosis induction was addressed by using flow cytometry to evaluate annexin V expression. Treatment with physalin F (10 μM) increased the apoptotic population of PBMC in HAM/TSP subjects. Transmission electron microscopy analysis of PBMC showed that physalin F induced ultrastructural changes, such as pyknotic nuclei, damaged mitochondria, enhanced autophagic vacuole formation, and the presence of myelin-like figures. In conclusion, physalin F induces apoptosis of PBMC, decreasing the spontaneous proliferation and cytokine production caused by HTLV-1 infection.
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil.
authors.forename: Lorena A
authors.initials: LA
authors.lastname: Pinto
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil.
authors.forename: Cássio S
authors.initials: CS
authors.lastname: Meira
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Cristiane F
authors.initials: CF
authors.lastname: Villarreal
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Vannier-Santos
authors.affiliation: Farmanguinhos, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudia V C
authors.initials: CV
authors.lastname: de Souza
authors.affiliation: Farmanguinhos, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ivone M
authors.initials: IM
authors.lastname: Ribeiro
authors.affiliation: Farmanguinhos, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Therezinha C B
authors.initials: TC
authors.lastname: Tomassini
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão-Castro
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Center of Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, Brazil.
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.affiliation: Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil. Electronic address: grassi@bahia.fiocruz.br.
authors.forename: Maria F R
authors.initials: MF
authors.lastname: Grassi
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D015493:Paraparesis, Tropical Spastic / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D010718:Phosphatidylserines / Q000378:metabolism; D032321:Physalis / Q000737:chemistry*; D012632:Secosteroids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D010718:Phosphatidylserines; D012632:Secosteroids; C075425:physalin F
keywords: Apoptosis; HTLV-1; Immunosuppressive activity; PBMC; Physalin F