ABSTRACT
Bursa of Fabricius is the acknowledged vital humoral immune system for B cell differentiation and antibody production. To study the molecular mechanism underlying the effect of bursal-derived BP5, we used gene microarray to analyze the genomic expression profiling of BP5-treated hybridoma cells. BP5 exhibited an immunomodulatory effect on antibody production in hybridoma cells and induced alterations in the gene expression profiles related to the immune-related biological processes, such as T cell activation and proliferation, B cell activation, B cell-mediated immunity, and cytokines cytokine production involved in immune response. In addition, 26 biological pathways associated with immunomodulatory functions were regulated in BP5-treated hybridoma cells, in which p53 signal pathway played an important role in antitumor. Among these regulated genes, 12 differentially expressed genes were verified by qRT-PCR. The activation of p53 activity by BP5 was further confirmed by p53 luciferase reporter assay and p53 expression. Our data revealed that bursal-derived BP5 could regulate various immune-related cellular processes, including antitumor factor p53 signal pathway, perhaps partially accounting for the reported immunomodulatory roles and novel antiproliferation on tumor cells functions of bursal-derived bioactive factor BP5.
Subject(s)
Antineoplastic Agents/pharmacology , Hybridomas/drug effects , Peptides/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Chlorocebus aethiops , Drug Screening Assays, Antitumor , Gene Expression Profiling , HeLa Cells , Humans , Hybridomas/cytology , Hybridomas/metabolism , MCF-7 Cells , Mice , Mice, Inbred BALB C , Peptides/chemical synthesis , Peptides/chemistry , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Structure-Activity Relationship , Tumor Suppressor Protein p53/genetics , Vero CellsABSTRACT
The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. Here, we isolated a novel bursal pentapeptide I (BPP-I), LGPGP, from BF. BPP-I could play inhibition effect on MCF-7 but not on CEF or Vero cell proliferation in vitro, and enhance antitumor factor p53 protein expression. Also, BPP-I stimulated antibody production in a dose-dependent manner in hybridoma cell. Furthermore, BPP-I could induce various immune responses in mice immunization experiments, including increase antibody production and cytokines IL-4 and IFN-γ level, and induce T-cell immunophenotyping. These results suggest that BPP-I is a potential immunomodulator of antitumor and immunity. The study could provide some novel insights on the probable candidate reagent for the antitumor and immune improvement.
