Pentalinonsterol, a Constituent of Pentalinon andrieuxii, Possesses Potent Immunomodulatory Activity and Primes T Cell Immune Responses.

Autor: Oghumu S; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Varikuti S; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Saljoughian N; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Terrazas C; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Huntsman AC; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Parinandi NL; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Fuchs JR; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Kinghorn AD; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States., Satoskar AR; College of Public Health, §College of Pharmacy, and ∥Department of Microbiology, The Ohio State University , Columbus, Ohio 43210, United States.; Department of Pathology and ⊥Department of Internal Medicine, The Ohio State University Medical Center , Columbus, Ohio 43210, United States.
Jazyk: angličtina
Zdroj: Journal of natural products [J Nat Prod] 2017 Sep 22; Vol. 80 (9), pp. 2515-2523. Date of Electronic Publication: 2017 Sep 06.
DOI: 10.1021/acs.jnatprod.7b00445
Abstrakt: The use of natural products as adjuvants has emerged as a promising approach for the development of effective vaccine formulations. Pentalinonsterol (PEN) is a recently isolated compound from the roots of Pentalinon andrieuxii and has been shown to possess antileishmanial activity against Leishmania spp. The objective of this study was to examine the immunomodulatory properties of PEN and evaluate its potential as an adjuvant. Macrophages and bone-marrow-derived dendritic cells (BMDCs) were stimulated with PEN and tested for gene expression, cytokine production, and their ability to activate T cells in vitro. PEN was also evaluated for its ability to generate antigen-specific Th1 and Th2 responses in vivo, following ovalbumin (OVA) immunization using PEN as an adjuvant. The results obtained demonstrate that PEN enhances the expression of NF-κB and AP1 transcription factors, promotes gene expression of Tnfα, Il6, Nos2, and Arg1, and upregulates MHCII, CD80, and CD86 in macrophages. PEN also enhanced IL-12 production in BMDCs and promoted BMDC-mediated production of IFN-γ by T cells. Further, mice immunized with OVA and PEN showed enhanced antigen-specific Th1 and Th2 cytokines in their splenocytes and lymph node cells, as well as increased levels of IgG1 and IgG2 in their sera. Taken together, this study demonstrates that PEN is a potent immunomodulatory compound and potentially can be used as an adjuvant for vaccine development against infectious diseases.
Databáze: MEDLINE