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Conference Paper: Immunochemical characterization of tripterygium wilfordii (triptolide, triptonide and synthetic racemic derivatives) immunosuppressive properties in allogenic mixed lymphocyte reaction

TitleImmunochemical characterization of tripterygium wilfordii (triptolide, triptonide and synthetic racemic derivatives) immunosuppressive properties in allogenic mixed lymphocyte reaction
Authors
Issue Date2006
PublisherWiley-Blackwell Publishing Asia
Citation
Shanghai—Hong Kong International Liver Congress, Shanghai, China, 25–28 March 2006. In Journal of Gastroenterology and Hepatology, 2006, v. 21 n. S2, p. A219 How to Cite?
AbstractTripterygium wilfordii (TW) has been used as immunosuppressant inorgan transplantation to prolong graft survival attributing to its anti-inflammatory and immunomodulating properties. Because of poten-tial cytotoxicity and unwanted side effects, practical applications ofthe TW compounds are not widely accepted in clinical settings. Fur-thermore, the molecular basis of TW active component responsiblefor immunomodulatory activity has not been fully elucidated. Thepresent study aims to characterize the functional constituents that areconferring the immunosuppressive effect in the established allogenicrat mixed lymphocyte reaction (MLR). High-responder inbred strainsof Lewis and Dark Agouti (DA) rats were used, and their splenocyteswere cocultured in triplicates at 2 × 105cells per well. After addingvariable concentrations of TW active components (triptolide, trip-tonide and their synthetic racemic derivatives) for 48 hours, the cellswere pulsed with 1 µCi [3H] methylthymidine per well for 16 hours.The proliferative response was determined by measuring the incor-poration by direct β counting. Cells grown with Concanavalin A wereused as positive control. Cells grown with or without FK506 wereused as controls. The final concentration of DMSO has no effect onthe growth of cells. Results were expressed as mean ± SD and evalu-ated by one-way ANOVA (Dunnett’s test). Significant values wereconsidered at the level of P < 0.05. Our present findings showed thatthe γ-butyrolactone group was essential to the pharmacologic prop-erties of TW active components that were studied. In addition, theIC50observed in the T59 (racemic derivative of triptolide) and trip-tonide was significantly elevated as compared to the correspondingtriptolide. The data implied that spatial arrangement of the hydroxylgroup in the triptolide compound was important to the immunosup-pressive function of TW on lymphocyte proliferative response. Col-lectively, a potent but less toxic TW active constituent may bedesigned to enhance its clinical applicability in organ transplantationand/or immune modulation of inflammatory reactions.(Supported by Research Grants Council of Hong Kong: HKU7280/02M)
Persistent Identifierhttp://hdl.handle.net/10722/108344
ISSN
2015 Impact Factor: 3.322
2015 SCImago Journal Rankings: 1.190

 

DC FieldValueLanguage
dc.contributor.authorWong, KFen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorLuk, JMCen_HK
dc.date.accessioned2010-09-26T00:35:43Z-
dc.date.available2010-09-26T00:35:43Z-
dc.date.issued2006en_HK
dc.identifier.citationShanghai—Hong Kong International Liver Congress, Shanghai, China, 25–28 March 2006. In Journal of Gastroenterology and Hepatology, 2006, v. 21 n. S2, p. A219en_HK
dc.identifier.issn0815-9319-
dc.identifier.urihttp://hdl.handle.net/10722/108344-
dc.description.abstractTripterygium wilfordii (TW) has been used as immunosuppressant inorgan transplantation to prolong graft survival attributing to its anti-inflammatory and immunomodulating properties. Because of poten-tial cytotoxicity and unwanted side effects, practical applications ofthe TW compounds are not widely accepted in clinical settings. Fur-thermore, the molecular basis of TW active component responsiblefor immunomodulatory activity has not been fully elucidated. Thepresent study aims to characterize the functional constituents that areconferring the immunosuppressive effect in the established allogenicrat mixed lymphocyte reaction (MLR). High-responder inbred strainsof Lewis and Dark Agouti (DA) rats were used, and their splenocyteswere cocultured in triplicates at 2 × 105cells per well. After addingvariable concentrations of TW active components (triptolide, trip-tonide and their synthetic racemic derivatives) for 48 hours, the cellswere pulsed with 1 µCi [3H] methylthymidine per well for 16 hours.The proliferative response was determined by measuring the incor-poration by direct β counting. Cells grown with Concanavalin A wereused as positive control. Cells grown with or without FK506 wereused as controls. The final concentration of DMSO has no effect onthe growth of cells. Results were expressed as mean ± SD and evalu-ated by one-way ANOVA (Dunnett’s test). Significant values wereconsidered at the level of P < 0.05. Our present findings showed thatthe γ-butyrolactone group was essential to the pharmacologic prop-erties of TW active components that were studied. In addition, theIC50observed in the T59 (racemic derivative of triptolide) and trip-tonide was significantly elevated as compared to the correspondingtriptolide. The data implied that spatial arrangement of the hydroxylgroup in the triptolide compound was important to the immunosup-pressive function of TW on lymphocyte proliferative response. Col-lectively, a potent but less toxic TW active constituent may bedesigned to enhance its clinical applicability in organ transplantationand/or immune modulation of inflammatory reactions.(Supported by Research Grants Council of Hong Kong: HKU7280/02M)-
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Asia-
dc.relation.ispartofJournal of Gastroenterology and Hepatologyen_HK
dc.titleImmunochemical characterization of tripterygium wilfordii (triptolide, triptonide and synthetic racemic derivatives) immunosuppressive properties in allogenic mixed lymphocyte reactionen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailWong, KF: kwongfai@hotmail.comen_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailLuk, JMC: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityLuk, JMC=rp00349en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1746.2006.04408.x-
dc.identifier.hkuros117201en_HK
dc.identifier.volume21en_HK
dc.identifier.issueSuppl 2en_HK
dc.identifier.spage219en_HK

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