Immunoenhancing Effects of Cyclina sinensis Pentadecapeptide through Modulation of Signaling Pathways in Mice with Cyclophosphamide-Induced Immunosuppression

Our study aimed to investigate the immune-enhancing mechanism of the pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) in a cyclophosphamide (CTX)-induced murine model of immunosuppression. Our results showed that SCSP treatment significantly increased mouse body weight, immune organ indices, and the production of serum IL-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha in CTX-treated mice. In addition, SCSP treatment enhanced the proliferation of splenic lymphocytes and peritoneal macrophages, as well as phagocytosis of the latter in a dose-dependent manner. Moreover, SCSP elevated the phosphorylation levels of p38, ERK, JNK, PI3K and Akt, and up-regulated IKK alpha, IKK beta, p50 NF-kappa B and p65 NF-kappa B protein levels, while down-regulating I kappa B alpha protein levels. Our results indicate that SCSP has immune-enhancing activities, and that it can activate the MAPK/NF-kappa B and PI3K/Akt pathways to enhance immunity in CTX-induced immunosuppressed mice.