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http://dx.doi.org/10.4014/jmb.2203.03008

Deinococcus radiodurans R1 Lysate Induces Tolerogenic Maturation in Lipopolysaccharide-Stimulated Dendritic Cells and Protects Dextran Sulfate Sodium-Induced Colitis in Mice  

Song, Ha-Yeon (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Han, Jeong Moo (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Kim, Woo Sik (Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Ji Hee (Division of Pathogen Resource Management, Center for Vaccine Development Support, National Institute of Infectious Disease, National Institute of Health (NIH), Korea Disease Control and Prevention Agency)
Park, Woo Yong (Department of Pharmacology, College of Korean Medicine, Kyung Hee University)
Byun, Eui-Baek (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Byun, Eui-Hong (Department of Food Science and Technology, Kongju National University)
Publication Information
Journal of Microbiology and Biotechnology / v.32, no.7, 2022 , pp. 835-843 More about this Journal
Abstract
Deinococcus radiodurans is an extremophilic bacterium that can thrive in harsh environments. This property can be attributed to its unique metabolites that possess strong antioxidants and other pharmacological properties. To determine the potential of D. radiodurans R1 lysate (DeinoLys) as a pharmacological candidate for inflammatory bowel disease (IBD), we investigated the antiinflammatory activity of DeinoLys in bone marrow-derived dendritic cells (BMDCs) and a colitis mice model. Lipopolysaccharide (LPS)-stimulated BMDCs treated with DeinoLys exhibited alterations in their phenotypic and functional properties by changing into tolerogenic DCs, including strongly inhibited proinflammatory cytokines (TNF-α and IL-12p70) and surface molecule expression and activated DC-induced T cell proliferation/activation with high IL-10 production. These phenotypic and functional changes in BMDCs induced by DeinoLys in the presence of LPS were abrogated by IL-10 neutralization. Furthermore, oral administration of DeinoLys significantly reduced clinical symptoms against dextran sulfate sodium-induced colitis, including body weight loss, disease activity index, histological severity in colon tissue, and lower myeloperoxidase level in mice. Our results establish DeinoLys as a potential anti-inflammatory candidate for IBD therapy.
Keywords
Deinococcus radiodurans R1 lysates; anti-inflammatory activity; tolerogenic dendritic cells; interleukin-10; inflammatory bowel disease;
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1 Zhang W, Liao J, Li H, Dong H, Bai H, Yang A, et al. 2013. Reduction of inflammatory bowel disease-induced tumor development in IL-10 knockout mice with soluble epoxide hydrolase gene deficiency. Mol. Carcinog. 52: 726-738.   DOI
2 Cardoso A, Gil Castro A, Martins AC, Carriche GM, Murigneux V, Castro I, et al. 2018. The dynamics of interleukin-10-afforded protection during dextran sulfate sodium-induced colitis. Front. Immunol. 9: 400.
3 Daletos G, Ebrahim W, Ancheeva E, El-Neketi M, Song W, Lin W, et al. 2018. Natural products from deep-sea-derived fungi a new source of novel bioactive compounds? Curr. Med. Chem. 25: 186-207.   DOI
4 Matheu MP, Sen D, Cahalan MD, Parker I. 2008. Generation of bone marrow derived murine dendritic cells for use in 2-photon imaging. J. Vis. Exp. 9: 773.
5 Song HY, Sik Kim W, Kim JM, Bak DH, Moo Han J, Lim ST, et al. 2019. A hydroxyethyl derivative of chrysin exhibits antiinflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice. Int. Immunopharmacol. 77: 105958.
6 Hidalgo-Cantabrana C, Algieri F, Rodriguez-Nogales A, Vezza T, Martinez-Camblor P, Margolles A, et al. 2016. Effect of a ropy exopolysaccharide-producing Bifidobacterium animalis subsp. lactis strain orally administered on DSS-induced colitis mice model. Front. Microbiol. 7: 868.
7 Meers GK, Bohnenberger H, Reichardt HM, Luhder F, Reichardt SD. 2018. Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells. PLoS One 13: e0190846.
8 Thomson AW, Robbins PD. 2008. Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann. Rheum. Dis. 67 Suppl 3: iii90-96.
9 Joffre O, Nolte MA, Sporri R, Reis e Sousa C. 2009. Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunol. Rev. 227: 234-247.   DOI
10 Jenkins MK, Schwartz RH. 1987. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med. 165: 302-319.   DOI
11 Morante-Palacios O, Fondelli F, Ballestar E, Martinez-Caceres EM. 2021. Tolerogenic dendritic cells in autoimmunity and inflammatory diseases. Trends Immunol. 42: 59-75.   DOI
12 Eichele DD, Kharbanda KK. 2017. Dextran sodium sulfate colitis murine model: an indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J. Gastroenterol. 23: 6016-6029.   DOI
13 Comi M, Amodio G, Gregori S. 2018. Interleukin-10-producing DC-10 is a unique tool to promote tolerance via antigen-specific T regulatory type 1 cells. Front. Immunol. 9: 682.
14 Taylor A, Akdis M, Joss A, Akkoc T, Wenig R, Colonna M, et al. 2007. IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain-containing protein tyrosine phosphatase 1. J. Allergy Clin. Immunol. 120: 76-83.   DOI
15 Huang H, Dawicki W, Zhang X, Town J, Gordon JR. 2010. Tolerogenic dendritic cells induce CD4+ CD25hiFoxp3+ regulatory T cell differentiation from CD4+ CD25-/loFoxp3- effector T cells. J. Immunol. 185: 5003-5010.   DOI
16 Frick JS, Zahir N, Muller M, Kahl F, Bechtold O, Lutz MB, et al. 2006. Colitogenic and non-colitogenic commensal bacteria differentially trigger DC maturation and Th cell polarization: an important role for IL-6. Eur. J. Immunol. 36: 1537-1547.   DOI
17 Volz T, Skabytska Y, Guenova E, Chen KM, Frick JS, Kirschning CJ, et al. 2014. Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells. J. Invest. Dermatol. 134: 96-104.   DOI
18 Mizoguchi A. 2012. Animal models of inflammatory bowel disease. Prog. Mol. Biol. Transl. Sci. 105: 263-320.   DOI
19 Jones-Hall YL, Grisham MB. 2014. Immunopathological characterization of selected mouse models of inflammatory bowel disease: comparison to human disease. Pathophysiology 21: 267-288.   DOI
20 Pedersen AE, Schmidt EG, Gad M, Poulsen SS, Claesson MH. 2009. Dexamethasone/1alpha-25-dihydroxyvitamin D3-treated dendritic cells suppress colitis in the SCID T-cell transfer model. Immunology 127: 354-364.   DOI
21 Choi YJ, Hur JM, Lim S, Jo M, Kim DH, Choi JI. 2014. Induction of apoptosis by deinoxanthin in human cancer cells. Anticancer Res. 34: 1829-1835.
22 Kim WS, Song HY, Mushtaq S, Kim JM, Byun EH, Yuk JM, et al. 2019. Therapeutic potential of gamma-irradiated resveratrol in ulcerative colitis via the anti-inflammatory activity and differentiation of tolerogenic dendritic cells. Cell. Physiol. Biochem. 52: 1117-1138.   DOI
23 Cabezon R, Benitez-Ribas D. 2013. Therapeutic potential of tolerogenic dendritic cells in IBD: from animal models to clinical application. Clin. Dev. Immunol. 2013: 789814.
24 Merino N, Aronson HS, Bojanova DP, Feyhl-Buska J, Wong ML, Zhang S, et al. 2019. Living at the extremes: extremophiles and the limits of life in a planetary context. Front. Microbiol. 10: 780.
25 Fucikova J, Palova-Jelinkova L, Bartunkova J, Spisek R. 2019. Induction of tolerance and immunity by dendritic cells: mechanisms and clinical applications. Front. Immunol. 10: 2393.
26 Obregon C, Kumar R, Pascual MA, Vassalli G, Golshayan D. 2017. Update on dendritic cell-induced immunological and clinical tolerance. Front. Immunol. 8: 1514.
27 Kim MK, Jang SA, Namkoong S, Lee JW, Park Y, Kim SH, et al. 2020. The Aqueous extract of radio-resistant Deinococcus actinosclerus BM2(T) suppresses lipopolysaccharide-mediated inflammation in RAW264.7 cells. J. Microbiol. Biotechnol. 30: 583-590.   DOI
28 Cox MM, Battista JR. 2005. Deinococcus radiodurans - the consummate survivor. Nat. Rev. Microbiol. 3: 882-892.   DOI
29 Slade D, Radman M. 2011. Oxidative stress resistance in Deinococcus radiodurans. Microbiol. Mol. Biol. Rev. 75: 133-191.   DOI
30 Maqbool I, Sudharsan M, Kanimozhi G, Alrashood ST, Khan HA, Prasad NR. 2020. Crude cell-free extract from Deinococcus radiodurans exhibit anticancer activity by inducing apoptosis in triple-negative breast cancer cells. Front. Cell Dev. Biol. 8: 707.
31 Lin SM, Baek CY, Jung JH, Kim WS, Song HY, Lee JH, et al. 2020. Antioxidant activities of an exopolysaccharide (DeinoPol) produced by the extreme radiation-resistant bacterium Deinococcus radiodurans. Sci. Rep. 10: 55.
32 Xiao TS. 2017. Innate immunity and inflammation. Cell Mol. Immunol. 14: 1-3.   DOI
33 Agrawal A, Agrawal S, Gupta S. 2017. Role of dendritic cells in inflammation and loss of tolerance in the elderly. Front. Immunol. 8: 896.
34 Audiger C, Rahman MJ, Yun TJ, Tarbell KV, Lesage S. 2017. The importance of dendritic cells in maintaining immune tolerance. J. Immunol. 198: 2223-2231.
35 Yoo S, Ha SJ. 2016. Generation of tolerogenic dendritic cells and their therapeutic applications. Immune Netw. 16: 52-60.   DOI
36 Gabani P, Singh OV. 2013. Radiation-resistant extremophiles and their potential in biotechnology and therapeutics. Appl. Microbiol. Biotechnol. 97: 993-1004.   DOI