The effects of suplatast tosilate (IPD-1151T) on innate immunity and antigen-presenting cells.
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.
Hsu
Li-Wen
LW
Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
Yang
Chin-Hsiang
CH
Goto
Shigeru
S
Nakano
Toshiaki
T
Lai
Chia-Yun
CY
Lin
Yu-Chun
YC
Kao
Ying-Hsien
YH
Chen
Shu-Hui
SH
Cheng
Yu-Fan
YF
Jawan
Bruno
B
Chiu
King-Wah
KW
Tsao
Fu-Kai
FK
Chen
Chao-Long
CL
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
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