Effects of 15-deoxyspergualin on proliferative responses and cytokine gene expression in vitro.
15-deoxyspergualin (DSG)-treated BALB/c spleen cells showed increased spontaneous proliferation and increased alloreactive mixed lymphocyte reactions (MLRs) when a 3-h treatment was carried out. However, when spleen cells were treated with DSG for 5 days without washing out DSG, decreased spontaneous proliferation was observed, although alloreactive MLRs against C3H/He and C57BL/6 alloantigens were increased. In contrast, cyclosporin A (CsA) induced markedly decreased alloreactive MLRs. Decreased concanavalin A (Con A)- and pokeweed mitogen (PWM)-induced responses were observed in spleen cells treated with DSG for 3 h; whereas increased phytohemagglutinin (PHA)-induced responses were observed. On the other hand, increased Con A- and PHA-induced responses were observed in spleen cells treated with DSG for 2 days, whereas PWM-induced responses were decreased. CsA-treatment induced markedly decreased mitogen-induced responses. These results suggest that the immunosuppressive mechanism of DSG differs from that of CsA. Reverse transcriptase-polymerase chain reaction (RT-PCR) method showed that interleukin 1 beta (IL-1 beta), IL-2, IL-3, IL-4, IL-5, and leukemia inhibitory factor (LIF) mRNA expression in DSG-treated spleen cells were increased by Con A stimulation, thus indicating that DSG modulates cytokine gene expression and inducing immunosuppressive mechanisms different from CsA.
Imamura
M
M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Japan.
Zhu
X
X
Hashino
S
S
Han
C W
CW
Tanaka
J
J
Kobayashi
H
H
Imai
K
K
Kasai
M
M
Sakurada
K
K
Miyazaki
T
T
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006146:Guanidines / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D017931:DNA Primers; D006146:Guanidines; D007166:Immunosuppressive Agents; D008934:Mitogens; D012333:RNA, Messenger; C037258:gusperimus