Role of interleukin-2 regulated proteins in immunosuppression by the N-alkylated prodigiosin analogue.
Prodigiosins have emerged as a novel family of tripyrrole compounds with significant T cell specific immunosuppressive potential. We had previously reported the immunosuppressive activity of a novel N-alkylated prodigiosin analogue, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1''-pyrryl)] dipyrryl-methene (MAMPDM) in mitogen stimulated spleen cells. There was an increase in the accumulation of IL-2 and induction of apoptotic cell death. Since IL-2 regulates both cellular proliferation and activation induced cell death (AICD), we have investigated the effect of MAMPDM on the expression of IL-2 regulated genes that are involved in these two opposite processes. The mitogen stimulated mouse spleen cells did not undergo a single division in presence of proliferation inhibitory concentrations of MAMPDM. An increase in the percentage of apoptotic cells was observed in the undivided cell population. The cells were arrested in G1 phase independent of the p53 expression. Expression of IL-2 regulated genes such as CD71, proliferating cell nuclear antigen (PCNA) and cyclin D was suppressed while that of Fas was not. Thus, in the presence of MAMPDM there was selective inhibition of only the pro-mitogenic signaling and not that of pro-apoptotic signaling by IL-2. The induction of apoptosis in presence of MAMPDM was the effect rather than cause for the anti-proliferative activity.
Pandey
Ruchi
R
Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Chander
Ramesh
R
Sainis
Krishna B
KB
D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D056741:Cyclin D; D016213:Cyclins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000502:physiology*; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011758:Pyrroles / Q000494:pharmacology*; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors; D019014:fas Receptor / Q000096:biosynthesis; D000099192:CD69 Antigens
D000475:Alkenes; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D056741:Cyclin D; D016213:Cyclins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D037181:Lectins, C-Type; D011353:Prodigiosin; D018809:Proliferating Cell Nuclear Antigen; D011758:Pyrroles; D011990:Receptors, Transferrin; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D000099192:CD69 Antigens; C477858:2,2'-(3-methoxy-1'amyl-5'-methyl-4-(1-pyrryl)) dipyrryl-methene; C068126:CD71 antigen