Melphalan-induced up-regulation of B7-1 surface expression on normal splenic B cells.

摘要: We have previously shown that exposure of MOPC-315 or P815 tumor cells to the widely used anticancer drug melphalan (L-PAM, L-phenylalanine mustard) leads rapid up-regulation B7–1 surface expression. Since B7–1-expressing depend on B7-expressing host antigen presenting (APC) for generation CD8+ T-cell-mediated antitumor immunity, and since L-PAM promotes acquisition tumor-eradicating immunity by T-cells from bearers, current studies were undertaken determine if also up-regulates expression APC. Here we show normal spleen within 24 h up-regulated B220+ (B cells). Studies into mechanism through which revealed 2 after L-PAM, accumulation mRNA is evident this requires de novo RNA synthesis, indicating regulation at transcriptional level. The L-PAM-induced was prevented with antioxidant N-acetyl-L-cysteine (NAC), reactive oxygen species are important regulation. Although AP-1 NF-κB considered redox-sensitive transcription factors, led only activation bound specifically a probe containing corresponding binding site in gene. Moreover, selective inhibition accumulation, essential gene cells. Finally, vivo administration an immunopotentiating dose mice found up-regulate their spleens. Thus, ability not but may contribute potentiating activity bearers.