title: Suppression of IL-2 production and proliferation of CD4(+) T cells by tuberostemonine O.
abstract: Tuberostemonine stereoisomers are natural alkaloids found in Stemona tuberosa, that are known to have anti-inflammatory and anti-infective properties. Tuberostemonine alkaloids inhibit inflammation by suppressing the expression of inflammatory mediators such as cyclooxygenase and nitric oxide synthase. However, the direct immunomodulatory properties of tuberostemonine alkaloids in T cells have not been elucidated so far. In this study, the activities in T cells of tuberostemonine N (TbN) and a novel alkaloid, tuberostemonine O (TbO), isolated from S. tuberosa, were investigated. Although TbN did not have a significant effect on cytokine production in splenic T cells, TbO selectively suppressed interleukin (IL)-2 production. Moreover, TbO, but not TbN, significantly inhibited IL-2 production by primary CD4(+) T cells and delayed the T-cell proliferation in a dose-dependent manner. Addition of excess recombinant IL-2 restored the decreased cell-division rates in TbO-treated CD4(+) T cells to control levels. Collectively, these findings suggest that the immunomodulatory effects of TbO occurred by the suppression of IL-2 expression and IL-2-induced T-cell proliferation, suggesting a potential beneficial role of tuberostemonine alkaloids for the control of chronic inflammatory and autoimmune diseases caused by hyperactivated T cells.
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120 - 750, Korea, (phone: +82-2-3277-4369; fax: +82-2-3277-3760).
authors.forename: Eun
authors.initials: E
authors.lastname: Jung Jang
authors.forename: Yun-Seo
authors.initials: YS
authors.lastname: Kil
authors.forename: Hye
authors.initials: H
authors.lastname: Ryeon Park
authors.forename: Sera
authors.initials: S
authors.lastname: Oh
authors.forename: Hyo
authors.initials: H
authors.lastname: Kyeong Kim
authors.forename: Mi
authors.initials: M
authors.lastname: Gyeong Jeong
authors.forename: Eun
authors.initials: E
authors.lastname: Kyoung Seo
authors.forename: Eun
authors.initials: E
authors.lastname: Sook Hwang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*
chemical_list: D000470:Alkaloids; D007376:Interleukin-2; C034243:tuberostemonine
keywords: Alkaloids; CD4+ T cells; Cell-division rates; IL-2 Production; Immunomodulatory activity; Stemona tuberosa; Tuberostemonine alkaloids