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

Mar Drugs. 2022 Aug 31;20(9):560. doi: 10.3390/md20090560.

Abstract

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-1β, and tumor necrosis factor (TNF)-α 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 IKKα, IKKβ, p50 NF-κB and p65 NF-κB protein levels, while down-regulating IκBα protein levels. Our results indicate that SCSP has immune-enhancing activities, and that it can activate the MAPK/NF-κB and PI3K/Akt pathways to enhance immunity in CTX-induced immunosuppressed mice.

Keywords: Cyclina sinensis; cyclophosphamide; immunomodulatory; mechanism; pentadecapeptide.

MeSH terms

  • Animals
  • Cyclophosphamide / toxicity
  • I-kappa B Kinase* / metabolism
  • I-kappa B Kinase* / pharmacology
  • Immunosuppression Therapy
  • Interleukin-6
  • Mice
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Cyclophosphamide
  • Proto-Oncogene Proteins c-akt
  • I-kappa B Kinase