Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR2 and TNF-α expression in mice

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Title: Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR2 and TNF-α expression in mice
Authors: Taghavi, M
Mortaz, E
Khosravi, A
Vahedi, G
Folkerts, G
Varahram, M
Kazempour-Dizaji, M
Garssen, J
Adcock, IM
Item Type: Journal Article
Abstract: Background : Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural - based treatments. Toll - like receptors (TLRs) play an important role in evoking innate immunity agains t cancer cells. Zymosan, a known TLR - 2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae - derived z ymosan - modulated skin melanoma progression by regulation of TLR - 2 expression in peritoneal macrophages and serum TNF -  level. Methods: Male C57BL/6 mice were divided into four groups: i) zymosan - treated (Z), ii) Melanoma - bearing mice (M), iii) Melanoma - bearing mice treated with zymosan (ZM) and iv) a healthy control group (negative control). 15 days after melanoma induction, mice were injected i.p. with zymosan (10  g) daily for 4 consecutive days. Mice were CO 2 - euthanized and serum TNF - α level, TLR - 2 expression in peritoneal macrophages and tumor gro wth measured. Splenocytes were treated ex - vivo with zymosan to determine viability and proliferation. Results: Tumor weight significantly decreased following therapeutic dosing with zymosan ( P <0.05). This was associated with zymosan - induced upregulation of TLR - 2 and TNF -  mRNA in peritoneal mac rophages and enhanced serum TNF -  levels ( P <0.05). Splenocyte number and viability were increased in a concentration - dependent manner by zymosan. Conclusion s : Our study suggests that zymosan - induced upregulation of TL R - 2 and TNF -  gene expression and of TNF -  release ; together with increased level s of lymphocyte proliferation may play a role in the inhibition of melanoma progression.
Issue Date: 22-Mar-2018
Date of Acceptance: 10-Mar-2018
URI: http://hdl.handle.net/10044/1/57887
DOI: https://dx.doi.org/10.1186/s12950-018-0182-y
ISSN: 1078-7852
Publisher: Springer Nature
Journal / Book Title: Journal of inflammation
Volume: 15
Copyright Statement: © The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 093080/Z/10/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
TLR-2
TLR-4
TNF-alpha
Zymosan
CYTOKINE PRODUCTION
IMMUNE-RESPONSES
CANCER-TREATMENT
BETA-GLUCANS
ACTIVATION
RECEPTOR
CELLS
INNATE
SKIN
PARTICULATE
TLR-2
TLR-4
TNF-α
Zymosan
1103 Clinical Sciences
1115 Pharmacology And Pharmaceutical Sciences
Immunology
Publication Status: Published
Article Number: ARTN 5
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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