Unveiling Immunomodulatory Effects of Euglena gracilis in Immunosuppressed Mice: Transcriptome and Pathway Analysis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
The immunomodulatory effects of Euglena gracilis (Euglena) and its bioactive component, β-1,3- glucan (paramylon), have been clarified through various studies. However, the detailed mechanisms of the immune regulation remain to be elucidated. This study was designed not only to investigate the immunomodulatory effects but also to determine the genetic mechanisms of Euglena and βglucan in cyclophosphamide (CCP)-induced immunosuppressed mice. The animals were orally administered saline, Euglena (800 mg/kg B.W.) or β-glucan (400 mg/kg B.W.) for 19 days, and CCP (80 mg/kg B.W.) was subsequently administered to induce immunosuppression in the mice. The mice exhibited significant decreases in body weight, organ weight, and the spleen index. However, there were significant improvements in the spleen weight and the spleen index in CCP-induced mice after the oral administration of Euglena and β-glucan. Transcriptome analysis of the splenocytes revealed immune-related differentially expressed genes (DEGs) regulated in the Euglena- and β-glucantreated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that pathways related with interleukin (IL)-17 and cAMP play significant roles in regulating T cells, B cells, and inflammatory cytokines. Additionally, Ptgs2, a major inflammatory factor, was exclusively expressed in the Euglena-treated group, suggesting that Euglena’s beneficial components, such as carotenoids, could regulate these genes by influencing immune lymphocytes and inflammatory cytokines in CCP-induced mice. This study validated the immunomodulatory effects of Euglena and highlighted its underlying mechanisms, suggesting a positive contribution to the determination of phenotypes associated with immune-related diseases and the research and development of immunotherapies.
Abstract
The immunomodulatory effects of Euglena gracilis (Euglena) and its bioactive component, β-1,3- glucan (paramylon), have been clarified through various studies. However, the detailed mechanisms of the immune regulation remain to be elucidated. This study was designed not only to investigate the immunomodulatory effects but also to determine the genetic mechanisms of Euglena and βglucan in cyclophosphamide (CCP)-induced immunosuppressed mice. The animals were orally administered saline, Euglena (800 mg/kg B.W.) or β-glucan (400 mg/kg B.W.) for 19 days, and CCP (80 mg/kg B.W.) was subsequently administered to induce immunosuppression in the mice. The mice exhibited significant decreases in body weight, organ weight, and the spleen index. However, there were significant improvements in the spleen weight and the spleen index in CCP-induced mice after the oral administration of Euglena and β-glucan. Transcriptome analysis of the splenocytes revealed immune-related differentially expressed genes (DEGs) regulated in the Euglena- and β-glucantreated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that pathways related with interleukin (IL)-17 and cAMP play significant roles in regulating T cells, B cells, and inflammatory cytokines. Additionally, Ptgs2, a major inflammatory factor, was exclusively expressed in the Euglena-treated group, suggesting that Euglena’s beneficial components, such as carotenoids, could regulate these genes by influencing immune lymphocytes and inflammatory cytokines in CCP-induced mice. This study validated the immunomodulatory effects of Euglena and highlighted its underlying mechanisms, suggesting a positive contribution to the determination of phenotypes associated with immune-related diseases and the research and development of immunotherapies.
참고문헌 (49)
- Piovan A, "Carotenoid extract derived from Euglena gracilis overcomes lipopolysaccharide-induced neuroinflammation in microglia : role of NF-κB and Nrf2 signaling pathways", Mol. Neurobiol, 58, pp.3515~3528 (2021)
- Nakashima A, "Antiviral activity and underlying action mechanism of Euglena extract against influenza virus", Nutrients, 13, pp.3911~ (2021)
- Kondo Y, "Cytokine-related immunopotentiating activities of paramylon, aβ-(1→3)-D-glucan from Euglena gracilis", J. Pharmacobiodyn, 15, pp.617~621 (1992)
- Barsanti L, "Paramylon (β-1,3-glucan) content in wild type and WZSL mutant of Euglena gracilis. Effects of growth conditions", J. Appl. Phycol, 13, pp.59~65 (2001)
- Gissibl A, "Bioproducts from Euglena gracilis : synthesis and applications", Front. Bioeng. Biotechnol, 7, pp.108~ (2019)
- Sugiyama A, "Oral administration of paramylon, a beta-1, 3-D-glucan isolated from Euglena gracilis Z inhibits development of atopic dermatitis-like skin lesions in NC", Nga mice, 2010, pp.72, 755~763
- Okouchi R, "Simultaneous intake of Euglena gracilis and vegetables exerts synergistic anti-obesity and anti-inflammatory effects by modulating the gut microbiota in diet-induced obese mice", Nutrients, 11, pp.204~ (2019)
- Yang H, "Immunoenhancing effects of Euglena gracilis on a cyclophosphamideinduced immunosuppressive mouse model", J. Microbiol. Biotechnol, 32, pp.228~237 (2022)
- Park S, "Euglena gracilis(Euglena)powder supplementation enhanced immune function through natural killer cell activity in apparently healthy participants : a randomized, double-blind, placebo-controlled trial", Nutr. Res, 119, pp.90~97 (2023)
- Jo KA, "Evaluation of the effects of Euglena gracilis on enhancing immune responses in RAW264.7 cells and a cyclophosphamide-induced mouse model", J. Microbiol. Biotechnol, 33, pp.493~499 (2023)
- Maggini S, "Feeding the immune system: the role of micronutrients in restoring resistance to infections", CABI Reviews (2008)[DOI]
- Germic N, "Regulation of the innate immune system by autophagy : monocytes, macrophages, dendritic cells and antigen presentation", Cell Death Differ, 26, pp.715~727 (2019)
- Gottschalk RA, "Distinct NF-κB and MAPK activation thresholds uncouple steady-state microbe sensing from anti-pathogen inflammatory responses", Cell Syst, 2, pp.378~390 (2016)
- Fink LN, "Dendritic cells from Peyer’s patches and mesenteric lymph nodes differ from spleen dendritic cells in their response to commensal gut bacteria", Scand. J. Immunol, 68, pp.270~279 (2008)
- Keely S, "Immune dysregulation in the functional gastrointestinal disorders", Eur. J. Clin. Investig, 45, pp.1350~1359 (2015)
- Rerknimitr P, "The etiopathogenesis of atopic dermatitis : barrier disruption, immunological derangement, and pruritus", Inflamm. Regen, 37, pp.14~ (2017)
- Luebke RW, "Suppression of immune function and susceptibility to infections in humans : association of immune function with clinical disease", J. Immunotoxicol, 1, pp.15~24 (2004)
- Shirani K, "Phytotrapy of cyclophosphamide-induced immunosuppression", Environ. Toxicol. Pharmacol, 39, pp.1262~1275 (2015)
- Meng Y, "Immunomodulatory activity of Lactobacillus plantarum KLDS1.0318 in cyclophosphamide-treated mice", Food Nutr. Res, 21, pp.62~ (2018)
- Jimenez-Valera M, "Modification of mitogen-driven lymphoproliferation by ceftriaxone in normal and immunocompromised mice", Int. J. Antimicrob. Agents, 22, pp.607~612 (2003)
- Bendich A, "Effect of beta-carotene and canthaxanthin on the immune responses of the rat", J. Nutr, 116, pp.2254~2262 (1986)
- Sudhagar A, "Transcriptome analysis based on RNA-Seq in understanding pathogenic mechanisms of diseases and the immune system of fish : a comprehensive review", Int. J. Mol. Sci, 19, pp.245~ (2018)
- Harding JJ, "Prospective genotyping of Hepatocellular Carcinoma : clinical implications of next-generation sequencing for matching patients to targeted and immune therapies", Clin. Cancer Res, 25, pp.2116~2126 (2019)
- Dheilly NM, "No more non-model species : the promise of next generation sequencing for comparative immunology", Dev. Compar. Immunol, 45, pp.56~66 (2014)
- Bray NL, "Near-optimal probabilistic RNA-seq quantification", Nat. Biotechnol, 34, pp.525~527 (2016)
- Sherman BT, "DAVID : a web server for functional enrichment analysis and functional annotation of gene lists(2021 update)", Nucleic Acids Res, 50, pp.W216~w221 (2022)
- Szklarczyk D, "STRING v11 : protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets", Nucleic Acids Res, 47, pp.D607~d613 (2019)
- Shannon P, "Cytoscape : a software environment for integrated models of biomolecular interaction networks", Genome Res, 13, pp.2498~2504 (2003)
- Binns D, "QuickGO : a web-based tool for gene ontology searching", Bioinformatics, 25, pp.3045~3046 (2009)
- Chen J, "The application of fungal β-glucans for the treatment of colon cancer", Anticancer Agents Med. Chem, 13, pp.725~730 (2013)
- Wang J, "Immuno-enhancement effects of Shenqi Fuzheng injection on cyclophosphamide-induced immunosuppression in Balb", c mice, 2012, pp.139, 788~795
- Williams MB, "Homing of naive and memory T lymphocyte subsets to Peyer's patches, lymph nodes, and spleen", J. Immunol, 159, pp.1746~1752 (1997)
- Casamassimi A, "Transcriptome profiling in human diseases : new advances and perspectives" (2017), 1652
- Suzuki K, "Euglena gracilis Z and its carbohydrate storage substance relieve arthritis symptoms by modulating Th17 immunity", PLoS One, 13, pp.e0191462~ (2018)
- Pandya AD, "Identification of human NK17", NK1 cells, 2011, pp.6, e26780~
- Huang L, "OX40L induces helper T cell differentiation during cell immunity of asthma through PI3K", AKT and P38 MAPK signaling pathway, 2018, pp.16, 74~
- Wolken J, "The relationship between chlorophyll and the carotenoids in the algal flagellate, Euglena", J. Gen. Physiol, 39, pp.675~ (1956)
- Foletta VC, "Transcriptional regulation in the immune system : all roads lead to AP-1", J. Leukoc. Biol, 63, pp.139~152 (1998)
- Wang X, "Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis", Clin. Exp. Immunol, 203, pp.194~208 (2021)
- Kelley JM, "Does gamma-aminobutyric acid(GABA)influence the development of chronic inflammation in rheumatoid arthritis?", J. Neuroinflammation, 5, pp.1~ (2008)
- Bhandage AK, "GABAergic signaling by cells of the immune system : more the rule than the exception", Cell. Mol. Life Sci, 78, pp.5667~5679 (2021)
- Cai W, "Identification of key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis", PeerJ, 8, pp.e8390~ (2020)
- Monmai C, "Immuno-enhancement effect of polysaccharide extracted from Stichopus japonicus on cyclophosphamide-induced immunosuppression mice", Food Sci. Biotechnol, 27, pp.565~573 (2018)
- Lin X, "Colonic epithelial mTORC1 promotes ulcerative colitis through COX-2-mediated Th17 responses", Mucosal Immunol, 11, pp.1663~1673 (2018)
- Calvayrac R, "Paramylon synthesis by Euglena gracilis photoheterotrophically grown under low O2 pressure", Planta, 153, pp.6~13 (1981)
- Bendich A, "Carotenoids and the immune response", J. Nutr, 119, pp.112~115 (1989)
- Yao R, "Carotenoids biosynthesis, accumulation, and applications of a model microalga Euglenagracilis", Mar. Drugs, 20, pp.496~ (2022)
- Pyo MY, "Pheophytin a and chlorophyll a identified from environmentally friendly cultivation of green pepper enhance interleukin-2 and interferon-γ in Peyer’s patches ex vivo Biol", Pharm. Bull, 36, pp.1747~1753 (2013)
- Piovan A, "Carotenoid extract derived from Euglena gracilis overcomes lipopolysaccharide-induced neuroinflammation in microglia : role of NF-κB and Nrf2 signaling pathways", Mol. Neurobiol, 58, pp.3515~3528 (2021)