Selective immunosuppression of prodigiosin 25-C and FK506 in the murine immune system.
The immunosuppressive effects of prodigiosin 25-C were studied in comparison with FK506. Both prodigiosin 25-C and FK506 suppressed T cell proliferation in response to concanavalin A (con A) or phytohemagglutinin (PHA) more significantly than that to lipopolysaccharide. However, prodigiosin 25-C inhibited con A-mediated mitogenic response more strongly than PHA-mediated one. FK506 showed no selectivity among those responses. In addition, when higher concentration of con A was used an inhibitory effect of prodigiosin 25-C became more evident whereas that of FK506 became less evident. Furthermore, prodigiosin 25-C affected neither interleukin-2 (IL-2) production nor IL-2 receptor (IL-2R) and transferrin receptor (TF-R) expression in vitro, though FK506 extensively inhibited IL-2 production and significantly suppressed IL-2R and TF-R expression. When comparing the effects of prodigiosin 25-C and FK506 in vivo by injecting antigens of different nature to a mouse, prodigiosin 25-C selectively inhibited cytotoxic T lymphocyte (CTL) activity induced by an allogenic mastocytoma, P815, without affecting production of antibody against a thymus dependent (TD) antigen, sheep red blood cell (SRBC). On the contrary, FK506 significantly inhibited both CTL induction and the antibody production. When Brucella abortus, a thymus independent (TI) antigen, and SRBC were simultaneously challenged to a mouse, neither prodigiosin 25-C nor FK506 affected antibody production against the TI antigen while the effect on the TD antigen were the same as described above. The present results revealed the unique immunosuppressive property of prodigiosin 25-C which was different from that of FK506.
Tsuji
R F
RF
Department of Agricultural Chemistry, University of Tokyo, Japan.
Yamamoto
M
M
Nakamura
A
A
Kataoka
T
T
Magae
J
J
Nagai
K
K
Yamasaki
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects; D000954:Antigens, Surface / Q000096:biosynthesis; D005260:Female; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011353:Prodigiosin / Q000494:pharmacology*; D051381:Rats; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011353:Prodigiosin; D016559:Tacrolimus