title: Effects of arsenic disulfide on proliferation, cytokine production, and frequencies of CD4(+), CD8(+), and regulatory T cells in mitogen-activated human peripheral blood mononuclear cells.
abstract: Influence of arsenic disulfide (As2S2) on human immune cells has little been investigated. Effects of As2S2 on proliferation, cytokine production, and frequencies of CD4(+) T, CD8(+) T and CD4(+)CD25(+)Foxp3(+) regulatory T cells in mitogen-activated human peripheral blood mononuclear cells were examined. Anti-proliferative effects of As2S2 on peripheral blood mononuclear cells activated by T-cell mitogen were assessed by a colorimetric assay. Cytokine concentrations in the culture medium were measured with beads-array procedures followed by flow cytometry. CD4(+) T cells, CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells were stained with fluorescence-labeled specific antibodies followed by flow cytometry analysis. As2S2 at 1-10μM significantly suppressed mitogen-activated proliferation of peripheral blood mononuclear cells (p<0.05). As2S2 at 10μM inhibited production of IL-6, -10, -17A, tumor necrosis factor-α, and interferon-γ from the activated peripheral blood mononuclear cells, though the effects were not statistically significant. As2S2 at 10μM significantly suppressed the frequencies of CD4(+) T and CD8(+) T cells (p<0.05), whereas significantly enhanced the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (p<0.05). The data suggest that As2S2 attenuates T cell-mediated immunity by not only suppressing the proliferation of T cells and cytokine release but also increasing the frequency of regulatory T cells. T cell-mediated autoimmunity contributes to bone marrow failure in myelodysplastic syndrome (MDS), and thus the above As2S2 effects are beneficial for the treatment of MDS patients.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; National Therapeutic Center of Hematology of Traditional Chinese Medicine, XiYuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, PR China; Beijing University of Chinese Medicine, Beijing, 100091, PR China.
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Song
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan; National Therapeutic Center of Hematology of Traditional Chinese Medicine, XiYuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, PR China.
authors.forename: Su
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Kiyomi
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Onda
authors.affiliation: Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy & Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Takagi
authors.affiliation: National Therapeutic Center of Hematology of Traditional Chinese Medicine, XiYuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, PR China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: hiranot@toyaku.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000328:Adult; D001152:Arsenicals / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects*; D013440:Sulfides / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
chemical_list: D001152:Arsenicals; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D008934:Mitogens; D013440:Sulfides; C058317:arsenic disulfide
keywords: Arsenic disulfide; CD4(+) T cells; CD4(+)CD25(+)Foxp3(+) regulatory T cells; CD8(+) T cells; Cytokines; Human peripheral blood mononuclear cells