The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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

References

  1. Melphalan-induced up-regulation of B7-1 surface expression on normal splenic B cells. Donepudi, M., Jovasevic, V.M., Raychaudhuri, P., Mokyr, M.B. Cancer Immunol. Immunother. (2003) [Pubmed]
 
WikiGenes - Universities