Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy

被引：36

作者：

Pinto, Lorena A. ^{[1
]}

Meira, Cassio S. ^{[1
]}

Villarreal, Cristiane F. ^{[1
,2
]}

Vannier-Santos, Marcos A. ^{[1
]}

de Souza, Claudia V. C. ^{[3
]}

Ribeiro, Ivone M. ^{[3
]}

Tomassini, Therezinha C. B. ^{[3
]}

Galvao-Castro, Bernardo ^{[1
,4
]}

Soares, Milena B. P. ^{[1
,5
]}

Grassi, Maria F. R. ^{[1
,4
]}

机构：

[1] Fiocruz MS, Goncalo Moniz Res Ctr CPqGM, Salvador, BA, Brazil

[2] Univ Fed Bahia, Salvador, BA, Brazil

[3] Fiocruz MS, Farmanguinhos, BR-21045900 Rio De Janeiro, RJ, Brazil

[4] Bahiana Sch Med & Publ Hlth, Salvador, BA, Brazil

[5] Sao Rafael Hosp, Ctr Biotechnol & Cell Therapy, Salvador, BA, Brazil

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2016年 / 79卷

关键词：

Physalin F; HTLV-1; PBMC; Immunosuppressive activity; Apoptosis; VIRUS TYPE-I; SPASTIC PARAPARESIS HAM/TSP; HTLV-1 PROVIRAL LOAD; INFECTION; TYPE-1; LEUKEMIA; MARKER; PROLIFERATION; TUBERCULOSIS; ACTIVATION;

D O I：

10.1016/j.biopha.2016.01.041

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 H-3-thymidine uptake. The IC50 for physalin F was 0.97 +/- 0.11 mu M. Flow cytometry analysis using Cytometric Bead Array (CBA) showed that physalin F (10 mM) significantly reduced the levels of IL-2, IL-6, IL-10, TNF-alpha and IFN-gamma, 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 mu M) 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. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：129 / 134

页数：6

共 34 条

[1] Quantifying HTLV-I dynamics [J].

Asquith, Becca ;

Bangham, Charles R. M. .

IMMUNOLOGY AND CELL BIOLOGY, 2007, 85 (04) :280-286

[2] Severe and Norwegian scabies are strongly associated with retroviral (HIV-1/HTLV-1) infection in Bahia, Brazil [J].

Brites, C ;

Weyll, M ;

Pedroso, C ;

Badaró, R .

AIDS, 2002, 16 (09) :1292-1293

[3] Activity of Physalin F in a Collagen-Induced Arthritis Model [J].

Brustolim, Daniele ;

Vasconcelos, Juliana F. ;

Freitas, Luiz Antonio R. ;

Teixeira, Mauro M. ;

Farias, Marcel T. ;

Ribeiro, Yvone M. ;

Tomassini, Therezinha C. B. ;

Oliveira, Geraldo G. S. ;

Pontes-de-Carvalho, Lain C. ;

Ribeiro-dos-Santos, Ricardo ;

Soares, Milena B. P. .

JOURNAL OF NATURAL PRODUCTS, 2010, 73 (08) :1323-1326

[4] Different cytokine production in tax-expressing cells between patients with human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis and asymptomatic HTLV-I carriers [J].

Furukawa, Y ;

Saito, M ;

Matsumoto, W ;

Usuku, K ;

Tanaka, Y ;

Izumo, S ;

Osame, M .

JOURNAL OF INFECTIOUS DISEASES, 2003, 187 (07) :1116-1125

[5]

GESSAIN A, 1985, LANCET, V2, P407

[6] Epidemiological aspects and world distribution of HTLV-1 infection [J].

Gessain, Antoine ;

Cassar, Olivier .

FRONTIERS IN MICROBIOLOGY, 2012, 3

[7] Resistance of CIN-positive T lymphocytes to etoposide-induced apoptosis mediated by upregulation of Bcl-xL expression in patients with HTLV-I-associated myelopathy [J].

Hamasaki, S ;

Nakamura, T ;

Furuya, T ;

Kawakami, A ;

Ichinose, K ;

Nakashima, T ;

Nishiura, Y ;

Shirabe, S ;

Eguchi, K .

JOURNAL OF NEUROIMMUNOLOGY, 2001, 117 (1-2) :143-148

[8] HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I INFECTION OF MONOCYTES AND MICROGLIAL CELLS IN PRIMARY HUMAN CULTURES [J].

HOFFMAN, PM ;

DHIBJALBUT, S ;

MIKOVITS, JA ;

ROBBINS, DS ;

WOLF, AL ;

BERGEY, GK ;

LOHREY, NC ;

WEISLOW, OS ;

RUSCETTI, FW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (24) :11784-11788

[9] Physalins from Witheringia solanacea as modulators off the NF-κB cascade [J].

Jacobo-Herrera, NJ ;

Bremner, P ;

Márquez, N ;

Gupta, MP ;

Gibbons, S ;

Muñoz, E ;

Heinrich, M .

JOURNAL OF NATURAL PRODUCTS, 2006, 69 (03) :328-331

[10] Physalins with anti-inflammatory activity are present in Physalis alkekengi var. franchetii and can function as Michael reaction acceptors [J].

Ji, Long ;

Yuan, Yonglei ;

Luo, Liping ;

Chen, Zhe ;

Ma, Xiaoqiong ;

Ma, Zhongjun ;

Cheng, Lin .

STEROIDS, 2012, 77 (05) :441-447

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