title: The effects of suplatast tosilate (IPD-1151T) on innate immunity and antigen-presenting cells.
abstract: We previously demonstrated that the anti-allergic drug, suplatast tosilate (IPD-1151T), prolonged rat survival after heterotopic heart transplantation (HHT) and suppressed mixed lymphocyte reaction (MLR). In the present study, we investigated the effects of suplatast on T cells, lipopolysaccharides (LPS), or peptidoglycan (PGN)-stimulated cells and dendritic cells (DCs). The addition of suplatast to concanavalin A (ConA) blasts inhibited the proliferation of cells in which the gene expression of T-helper-1 (Th1) and T-helper-2 (Th2) cytokines including interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 were down-regulated with decreased concentration of the IFN-gamma and IL-10 in the supernatants of ConA blast cells. Suplatast also showed down-regulation of the toll-like receptor (TLR)2, TLR4, and CD14 gene expressions on splenocytes stimulated by LPS and PGN, TLR2 or TLR4 agonist, respectively. DCs treated with suplatast expressed lower levels of CD40, CD80, and CD86 and reduced IL-12 production. These results suggest that suplatast may modulate the TLRs on antigen-presenting cells (APCs) and thus block the pathway of Th1/Th2 cytokine production.
authors.affiliation: Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Chin-Hsiang
authors.initials: CH
authors.lastname: Yang
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.forename: Bruno
authors.initials: B
authors.lastname: Jawan
authors.forename: King-Wah
authors.initials: KW
authors.lastname: Chiu
authors.forename: Fu-Kai
authors.initials: FK
authors.lastname: Tsao
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001190:Arylsulfonates / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013452:Sulfonium Compounds / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D001190:Arylsulfonates; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D013452:Sulfonium Compounds; D051193:Toll-Like Receptors; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C073028:suplatast tosilate