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Ranitidine as an adjuvant regulates macrophage polarization and activates CTLs through the PI3K-Akt2 signaling pathway.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2023 Mar; Vol. 116, pp. 109729. Date of Electronic Publication: 2023 Feb 16. - Publication Year :
- 2023
-
Abstract
- Adjuvants are an indispensable component of vaccines, but there are few adjuvants for human vaccines. H2 receptor blockers, inhibiting gastric acid secretion, have immune enhancement effects. Ranitidine (RAN) is a water-soluble H2 receptor blocker, and whether it has an immune-enhancing effect is still unknown. In this study, flow cytometry, western blotting, and immunofluorescence methods were used to analyze whether RAN could activate macrophage polarization to the M1 phenotype in vivo and in vitro. Here, we found that the M1 inflammatory cytokine levels and surface markers in RAW264.7 cells were upregulated by NF-κB activation, possibly through the PI3K-Akt2 signaling pathway, after RAN treatment. Endocytic function was also enhanced by feedback regulation of Akt2/GSK3β/Dynmin1 signaling. Furthermore, to evaluate the adjuvant function of RAN, we used OVA plus RAN as a vaccine to inhibit the growth of B16-OVA tumors in mice. We also found that in the RAN adjuvant group, macrophage polarization to M1, Th1 cell differentiation, and cytotoxic T lymphocyte (CTL) activation were significantly upregulated. The tumor growth of mice was inhibited, and the survival rate of mice was significantly improved. This study provides new evidence for the mechanism by which RAN activates the immune response and is expected to provide a new strategy for the research and development of tumor vaccine adjuvants.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
NF-kappa B metabolism
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
RAW 264.7 Cells
Signal Transduction
Vaccines
Macrophage Activation drug effects
Macrophage Activation immunology
Cancer Vaccines immunology
Cancer Vaccines therapeutic use
Adjuvants, Immunologic pharmacology
Adjuvants, Immunologic therapeutic use
Neoplasms drug therapy
Neoplasms immunology
Ranitidine pharmacology
Ranitidine therapeutic use
T-Lymphocytes, Cytotoxic drug effects
T-Lymphocytes, Cytotoxic immunology
Macrophages drug effects
Macrophages immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 116
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 37800555
- Full Text :
- https://doi.org/10.1016/j.intimp.2023.109729