Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice
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 against cancer cells. Zymosan,...
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12950-018-0182-y |
| _version_ | 1818893729969209344 |
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| author | Mehdi Taghavi Esmaeil Mortaz Alireza Khosravi Ghasem Vahedi Gert Folkerts Mohammad Varahram Mehdi Kazempour-Dizaji Johan Garssen Ian M. Adcock |
| author_facet | Mehdi Taghavi Esmaeil Mortaz Alireza Khosravi Ghasem Vahedi Gert Folkerts Mohammad Varahram Mehdi Kazempour-Dizaji Johan Garssen Ian M. Adcock |
| author_sort | Mehdi Taghavi |
| collection | DOAJ |
| description | 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 against 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 zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α 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 μg) daily for 4 consecutive days. Mice were CO2-euthanized and serum TNF-α level, TLR-2 and TLR-4 expression in peritoneal macrophages and tumor growth 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, TLR-4 and TNF-α mRNA in peritoneal macrophages and enhanced serum TNF-α levels (P < 0.05). Splenocyte number and viability were increased in a concentration-dependent manner by zymosan. Conclusions Our study suggests that zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α gene expression and of TNF-α release; together with increased level of lymphocyte proliferation may play a role in the inhibition of melanoma progression. |
| first_indexed | 2024-12-19T18:17:14Z |
| format | Article |
| id | doaj.art-fb7f1f03aa88435dbbf471362b9132d7 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-19T18:17:14Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-fb7f1f03aa88435dbbf471362b9132d72022-12-21T20:11:06ZengBMCJournal of Inflammation1476-92552018-03-0115111010.1186/s12950-018-0182-yZymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in miceMehdi Taghavi0Esmaeil Mortaz1Alireza Khosravi2Ghasem Vahedi3Gert Folkerts4Mohammad Varahram5Mehdi Kazempour-Dizaji6Johan Garssen7Ian M. Adcock8Mycology Research Center, Faculty of Veterinary Medicine, University of TehranDepartment of Immunology, Faculty of Medicine, ShahidBeheshti University of Medical SciencesMycology Research Center, Faculty of Veterinary Medicine, University of TehranMycology Research Center, Faculty of Veterinary Medicine, University of TehranDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht UniversityMycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical SciencesMycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical SciencesDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht UniversityAirways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College LondonAbstract 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 against 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 zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α 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 μg) daily for 4 consecutive days. Mice were CO2-euthanized and serum TNF-α level, TLR-2 and TLR-4 expression in peritoneal macrophages and tumor growth 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, TLR-4 and TNF-α mRNA in peritoneal macrophages and enhanced serum TNF-α levels (P < 0.05). Splenocyte number and viability were increased in a concentration-dependent manner by zymosan. Conclusions Our study suggests that zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α gene expression and of TNF-α release; together with increased level of lymphocyte proliferation may play a role in the inhibition of melanoma progression.http://link.springer.com/article/10.1186/s12950-018-0182-yTLR-2TLR-4TNF-αZymosan |
| spellingShingle | Mehdi Taghavi Esmaeil Mortaz Alireza Khosravi Ghasem Vahedi Gert Folkerts Mohammad Varahram Mehdi Kazempour-Dizaji Johan Garssen Ian M. Adcock Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice Journal of Inflammation TLR-2 TLR-4 TNF-α Zymosan |
| title | Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice |
| title_full | Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice |
| title_fullStr | Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice |
| title_full_unstemmed | Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice |
| title_short | Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice |
| title_sort | zymosan attenuates melanoma growth progression increases splenocyte proliferation and induces tlr 2 4 and tnf α expression in mice |
| topic | TLR-2 TLR-4 TNF-α Zymosan |
| url | http://link.springer.com/article/10.1186/s12950-018-0182-y |
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