Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR2 and TNF-α expression in mice
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Author(s)
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.
:
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.
Date Issued
2018-03-22
Date Acceptance
2018-03-10
Citation
Journal of inflammation, 2018, 15
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
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
Wellcome Trust
Grant Number
093080/Z/10/Z
Subjects
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
TNF-α
1103 Clinical Sciences
1115 Pharmacology And Pharmaceutical Sciences
Publication Status
Published
Article Number
ARTN 5