Inhibitory effects of suplatast tosilate on the differentiation and function of monocyte-derived dendritic cells from patients with asthma.
BACKGROUND
Dendritic cells (DCs) are antigen-presenting cells that efficiently activate T cells.


OBJECTIVE
We examined the effects of suplatast tosilate, which prevents T-helper type 2 responses, on the differentiation and function of monocyte-derived DCs (moDCs).


METHODS
DCs were differentiated in vitro from peripheral monocytes from patients with asthma by the addition of granulocyte macrophage colony-stimulating factor and IL-4 in the presence or absence of suplatast tosilate. Cell surface molecules (CD1a, CD14, CD80, CD83, CD86, HLA-DR) on immature and mature DCs were analysed with flow cytometry, and the secretion of CC chemokine ligand (CCL)17 (thymus and activation-regulated chemokine), IL-12p70, IL-12p40, and IL-10 was measured with an ELISA. We also studied the proliferative responses of allogeneic CD4(+) T cells from healthy subjects to DCs differentiated in the presence of suplatast tosilate. In addition, the production of IFN-gamma and IL-5 by CD4(+) T cells after coculture with untreated DCs or suplatast tosilate-treated DCs was measured with ELISA.


RESULTS
Suplatast tosilate significantly inhibited the expression of CD1a, CD80, and CD86 on immature DCs and of CD1a, CD80, CD83, and CD86 on mature DCs. Suplatast tosilate also significantly inhibited the secretion of CCL17, IL-12p70, and IL-12p40; however, the secretion of IL-10 was not affected. The proliferative responses of allogeneic CD4(+) T cells to suplatast tosilate-treated DCs were suppressed. Moreover, suplatast tosilate-treated DCs had an impaired capacity to stimulate CD4(+) T cells to produce IFN-gamma and IL-5.


CONCLUSIONS
Suplatast tosilate inhibits the differentiation, maturation, and function of moDCs.
Tanaka
A
A
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Minoguchi
K
K
Samson
K T R
KT
Oda
N
N
Yokoe
T
T
Tazaki
T
T
Yamamoto
Y
Y
Yamamoto
M
M
Ohta
S
S
Adachi
M
M
D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D001190:Arylsulfonates / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D013452:Sulfonium Compounds / Q000494:pharmacology* / Q000627:therapeutic use
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D015703:Antigens, CD; D001190:Arylsulfonates; C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; C508609:IL10 protein, human; C508599:IL5 protein, human; D053762:Interleukin-12 Subunit p40; D015848:Interleukin-5; D013452:Sulfonium Compounds; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C073028:suplatast tosilate