{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:55:31Z","timestamp":1740167731328,"version":"3.37.3"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T00:00:00Z","timestamp":1576886400000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773743"],"award-info":[{"award-number":["81773743"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20150590"],"award-info":[{"award-number":["BK20150590"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>T lymphocytes play an important role in contact hypersensitivity. This study aims to explore the immunosuppressive activity of SBF-1, an analog of saponin OSW-1, against T lymphocytes in vitro and in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Proliferation of T lymphocytes from lymph nodes of mice was determined by MTT assay. Flow cytometry analysis was performed to assess T cell activation and apoptosis. Levels of cytokines were determined by PCR and ELISA. BALB\/c mice were sensitized and challenged with picryl chloride and thickness of left and right ears were measured.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>SBF-1 effectively inhibited T lymphocytes proliferation induced by concanavalin A (Con A) or anti-CD3 plus anti-CD28 at a very low dose (10\u2009nM) but exhibited little toxicity in non-activated T lymphocytes at concentrations up to 10\u2009\u03bcM. In addition, SBF-1 inhibited the expression of CD25 and CD69, as well as he phosphorylation of AKT in Con A-activated T cells. SBF-1 also induced apoptosis of activated T cells. In addition, SBF-1 also downregulated the induction of the T cell cytokines, IL-2 and IFN-\u03b3 in a dose-dependent manner. Furthermore, SBF-1 significantly suppressed ear swelling and inflammation in a mouse model of picryl chloride-induced contact hypersensitivity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that SBF-1 has an unique immunosuppressive activity both in vitro and in vivo mainly through inhibiting T cell proliferation and activation. Its mechanism appears to be related to the blockage of AKT signaling pathway.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40360-019-0377-8","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T12:02:29Z","timestamp":1576929749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SBF-1 inhibits contact hypersensitivity in mice through down-regulation of T-cell-mediated responses"],"prefix":"10.1186","volume":"20","author":[{"given":"Wei","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianying","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"key":"377_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s10585-009-9253-z","volume":"26","author":"S Bhattacharyya","year":"2009","unstructured":"Bhattacharyya S, Tobacman JK. Arylsulfatase B regulates colonic epithelial cell migration by effects on MMP9 expression and RhoA activation. Clin Exp Metastasis. 2009;26:535\u201345.","journal-title":"Clin Exp Metastasis"},{"key":"377_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.bbrc.2017.12.159","volume":"496","author":"R Muro","year":"2018","unstructured":"Muro R, Nitta T, Kitajima M, Okada T, Suzuki H. Rasal3-mediated T cell survival is essential for inflammatory responses. Biochem Biophys Res Commun. 2018;496:25\u201330.","journal-title":"Biochem Biophys Res Commun"},{"key":"377_CR3","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1146\/annurev.immunol.021908.132706","volume":"27","author":"JE Smith-Garvin","year":"2009","unstructured":"Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591\u2013619.","journal-title":"Annu Rev Immunol"},{"key":"377_CR4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/nri.2016.80","volume":"16","author":"DE Speiser","year":"2016","unstructured":"Speiser DE, Ho PC, Verdeil G. Regulatory circuits of T cell function in cancer. Nat Rev Immunol. 2016;16:599\u2013611.","journal-title":"Nat Rev Immunol"},{"key":"377_CR5","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nrendo.2012.114","volume":"8","author":"H Sell","year":"2012","unstructured":"Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol. 2012;8:709\u201316.","journal-title":"Nat Rev Endocrinol"},{"key":"377_CR6","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.clinbiochem.2015.07.099","volume":"49","author":"E Wieland","year":"2016","unstructured":"Wieland E, Shipkova M. Lymphocyte surface molecules as immune activation biomarkers. Clin Biochem. 2016;49:347\u201354.","journal-title":"Clin Biochem"},{"key":"377_CR7","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/stem.5530120502","volume":"12","author":"SF Ziegler","year":"1994","unstructured":"Ziegler SF, Ramsdell F, Alderson MR. The activation antigen CD69. Stem Cells. 1994;12:456\u201365.","journal-title":"Stem Cells"},{"key":"377_CR8","first-page":"1031","volume":"43","author":"MH Flax","year":"1963","unstructured":"Flax MH, Caulfield JB. Cellular and vascular components of allergic contact dermatitis. Am J Pathol. 1963;43:1031\u201353.","journal-title":"Am J Pathol"},{"key":"377_CR9","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1016\/S1734-1140(13)71529-9","volume":"65","author":"K Curzytek","year":"2013","unstructured":"Curzytek K, Kubera M, Szczepanik M, Basta-Kaim A, Leskiewicz M, Budziszewska B, Lason W, Maes M. Crosstalk between contact hypersensitivity reaction and antidepressant drugs. Pharmacol Rep. 2013;65:1673\u201380.","journal-title":"Pharmacol Rep"},{"key":"377_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1034\/j.1600-0536.2002.460101.x","volume":"46","author":"I Kimber","year":"2002","unstructured":"Kimber I, Dearman RJ. Allergic contact dermatitis: the cellular effectors. Contact Dermatitis. 2002;46:1\u20135.","journal-title":"Contact Dermatitis"},{"key":"377_CR11","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1248\/bpb.b17-00594","volume":"41","author":"Y Fujimoto","year":"2018","unstructured":"Fujimoto Y, Fujita T, Kuramoto N, Kuwamura M, Izawa T, Nishiyama K, Yoshida N, Nakajima H, Takeuchi T, Azuma YT. The role of Interleukin-19 in contact hypersensitivity. Biol Pharm Bull. 2018;41:182\u20139.","journal-title":"Biol Pharm Bull"},{"key":"377_CR12","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/nri1204","volume":"3","author":"BD Kahan","year":"2003","unstructured":"Kahan BD. Individuality: the barrier to optimal immunosuppression. Nat Rev Immunol. 2003;3:831\u20138.","journal-title":"Nat Rev Immunol"},{"key":"377_CR13","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1586\/eri.10.178","volume":"9","author":"J Carbone","year":"2011","unstructured":"Carbone J, del Pozo N, Gallego A, Sarmiento E. Immunological risk factors for infection after immunosuppressive and biologic therapies. Expert Rev Anti-Infect Ther. 2011;9:405\u201313.","journal-title":"Expert Rev Anti-Infect Ther"},{"key":"377_CR14","doi-asserted-by":"publisher","first-page":"4324","DOI":"10.1002\/anie.200454237","volume":"43","author":"B Shi","year":"2004","unstructured":"Shi B, Wu H, Yu B, Wu J. 23-oxa-analogues of OSW-1: efficient synthesis and extremely potent antitumor activity. Angew Chem Int Ed Engl. 2004;43:4324\u20137.","journal-title":"Angew Chem Int Ed Engl"},{"key":"377_CR15","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.ijpharm.2004.03.016","volume":"278","author":"D Guggi","year":"2004","unstructured":"Guggi D, Langoth N, Hoffer MH, Wirth M, Bernkop-Schnurch A. Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate. Int J Pharm. 2004;278:353\u201360.","journal-title":"Int J Pharm"},{"key":"377_CR16","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.intimp.2016.08.025","volume":"40","author":"X Li","year":"2016","unstructured":"Li X, Wang X, Jiang H, Zhang G, Tan R, Sun Y, Wu X, Xu Q. Herpetol ameliorates allergic contact dermatitis through regulating T-lymphocytes. Int Immunopharmacol. 2016;40:131\u20138.","journal-title":"Int Immunopharmacol"},{"key":"377_CR17","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.taap.2010.12.011","volume":"251","author":"Q Luo","year":"2011","unstructured":"Luo Q, Gu Y, Zheng W, Wu X, Gong F, Gu L, Sun Y, Xu Q. Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf\/ERK cascade and Akt signaling pathway. Toxicol Appl Pharmacol. 2011;251:130\u20136.","journal-title":"Toxicol Appl Pharmacol"},{"key":"377_CR18","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/eji.201646837","volume":"47","author":"D Cibrian","year":"2017","unstructured":"Cibrian D, Sanchez-Madrid F. CD69: from activation marker to metabolic gatekeeper. Eur J Immunol. 2017;47:946\u201353.","journal-title":"Eur J Immunol"},{"key":"377_CR19","doi-asserted-by":"crossref","unstructured":"Pompura SL, Dominguez-Villar M. The PI3K\/AKT signaling pathway in regulatory T-cell development, stability, and function. J Leukoc Biol. 2018;","DOI":"10.1002\/JLB.2MIR0817-349R"},{"key":"377_CR20","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1097\/00041552-199805000-00010","volume":"7","author":"DL Perkins","year":"1998","unstructured":"Perkins DL. T-cell activation in autoimmune and inflammatory diseases. Curr Opin Nephrol Hypertens. 1998;7:297\u2013303.","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"377_CR21","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.bcp.2012.04.006","volume":"84","author":"W Li","year":"2012","unstructured":"Li W, Song R, Fang X, Wang L, Chen W, Tang P, Yu B, Sun Y, Xu Q. SBF-1, a synthetic steroidal glycoside, inhibits melanoma growth and metastasis through blocking interaction between PDK1 and AKT3. Biochem Pharmacol. 2012;84:172\u201381.","journal-title":"Biochem Pharmacol"},{"key":"377_CR22","doi-asserted-by":"publisher","first-page":"e1581","DOI":"10.1038\/cddis.2014.538","volume":"5","author":"W Li","year":"2014","unstructured":"Li W, Ouyang Z, Zhang Q, Wang L, Shen Y, Wu X, Gu Y, Shu Y, Yu B, Sun Y, et al. SBF-1 exerts strong anticervical cancer effect through inducing endoplasmic reticulum stress-associated cell death via targeting sarco\/endoplasmic reticulum Ca (2+)-ATPase 2. Cell Death Dis. 2014;5:e1581.","journal-title":"Cell Death Dis"},{"key":"377_CR23","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.canlet.2015.12.014","volume":"372","author":"A Elgehama","year":"2016","unstructured":"Elgehama A, Chen W, Pang J, Mi S, Li J, Guo W, Wang X, Gao J, Yu B, Shen Y, et al. Blockade of the interaction between Bcr-Abl and PTB1B by small molecule SBF-1 to overcome imatinib-resistance of chronic myeloid leukemia cells. Cancer Lett. 2016;372:82\u20138.","journal-title":"Cancer Lett"},{"key":"377_CR24","doi-asserted-by":"publisher","first-page":"e65413","DOI":"10.1371\/journal.pone.0065413","volume":"8","author":"K Radulovic","year":"2013","unstructured":"Radulovic K, Rossini V, Manta C, Holzmann K, Kestler HA, Niess JH. The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine. PLoS One. 2013;8:e65413.","journal-title":"PLoS One"},{"key":"377_CR25","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1053\/berh.2001.0187","volume":"15","author":"H Schulze-Koops","year":"2001","unstructured":"Schulze-Koops H, Kalden JR. The balance of Th1\/Th2 cytokines in rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2001;15:677\u201391.","journal-title":"Best Pract Res Clin Rheumatol"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-019-0377-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40360-019-0377-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-019-0377-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T00:17:21Z","timestamp":1608423441000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-019-0377-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["377"],"URL":"https:\/\/doi.org\/10.1186\/s40360-019-0377-8","relation":{},"ISSN":["2050-6511"],"issn-type":[{"type":"electronic","value":"2050-6511"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"19 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The experimental processes including the protocols in this study were approved by the medical ethical committee of Nanjing University.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}