{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:18:21Z","timestamp":1777522701408,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T00:00:00Z","timestamp":1534982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003668","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries","doi-asserted-by":"publisher","award":["316051-03-3-HD020"],"award-info":[{"award-number":["316051-03-3-HD020"]}],"id":[{"id":"10.13039\/501100003668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Production of oligosaccharides from Leuconostoc lactis CCK940 was optimized using a response surface methodology with a central composite design. Culture temperature and the concentrations of sucrose and maltose were used as the main factors. The predicted optimum conditions for the production of oligosaccharides were a culture temperature of 30 \u00b0C, a sucrose concentration of 9.6% (w\/v), and a maltose concentration of 7.4% (w\/v). Using these optimal conditions, Leuconostoc lactis CCK940 was cultured using a fermenter to produce oligosaccharides, and the resulting oligosaccharides with a degree of polymerization greater than 4 were purified by Bio-gel P2 gel permeation column chromatography and then lyophilized. When macrophages were treated with the purified oligosaccharides at concentrations of 0.1\u201310 mg\/mL, no cytotoxicity towards the macrophages was observed. However, nitric oxide production levels were similar to those following treatment with 1 \u03bcg\/mL lipopolysaccharide. The mRNA expression levels of tumor necrosis factor-\u03b1, interleukin-1\u03b2, interleukin-6, and inducible nitric oxide synthase were all also increased in a dose-dependent manner following treatment with the oligosaccharides. These data suggest that oligosaccharides produced by Leuconostoc lactis CCK940 could be used as an immune enhancer of macrophages.<\/jats:p>","DOI":"10.3390\/molecules23092118","type":"journal-article","created":{"date-parts":[[2018,8,24]],"date-time":"2018-08-24T03:42:31Z","timestamp":1535082151000},"page":"2118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Optimization of Oligosaccharide Production from Leuconostoc lactis Using a Response Surface Methodology and the Immunostimulating Effects of These Oligosaccharides on Macrophage Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9481-128X","authenticated-orcid":false,"given":"Sulhee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Food Science and Biotechnology, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwi-Gun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Kweon","family":"Jang","sequence":"additional","affiliation":[{"name":"Food Nutrition Major, School of Food, Chungkang College of Cultural Industries, Icheon 17390, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-4201","authenticated-orcid":false,"given":"Young-Seo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.fbp.2016.01.013","article-title":"Oligosaccharide synthesis in fruit juice concentrates using a glucansucrase from Lactobacillus reuteri 180","volume":"98","author":"Johansson","year":"2016","journal-title":"Food Bioprod. Process."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ijbiomac.2016.05.019","article-title":"Leuconostoc citreum SK24.002 glucansucrase: Biochemical characterisation and de novo synthesis of \u03b1-glucan","volume":"91","author":"Song","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1007\/s13213-015-1072-7","article-title":"Hyper glucansucrase, glucan and oligosaccharide producing novel Weissella cibaria RBA12 isolated from Pummelo (Citrus maxima)","volume":"65","author":"Baruah","year":"2015","journal-title":"Ann. Microbiol."},{"key":"ref_4","first-page":"259","article-title":"Enzymatic synthesis of fructo-oligosaccharides by recombinant levansucrase from Leuconostoc mesenteroides Lm17","volume":"49","author":"Salim","year":"2017","journal-title":"Bulg. Chem. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0008-6215(01)00038-6","article-title":"Novel oligosaccharides synthesized from sucrose donor and cellobiose acceptor by alternansucrase","volume":"331","author":"Willemot","year":"2001","journal-title":"Carbohydr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.1016\/j.biortech.2008.01.032","article-title":"Screening and optimization of nutritional factors for higher dextransucrase production by Leuconostoc mesenteroides NRRL B-640 using statistical approach","volume":"99","author":"Purama","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.carbpol.2017.06.021","article-title":"Optimization of dextran production by Weissella cibaria NITCSK4 using Response Surface Methodology-Genetic Algorithm based technology","volume":"174","author":"Kanimozhi","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/sj.jim.7000319","article-title":"Optimization of galacto-oligosaccharide production by Bifidobacterium infantis RW-8120 using response surface methodology","volume":"29","author":"Roy","year":"2002","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0008-6215(82)85013-1","article-title":"Acceptor reactions of alternansucrase from Leuconostoc mesenteroides NRRL B-1355","volume":"111","author":"Robyt","year":"1982","journal-title":"Carbohydr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0008-6215(83)84024-5","article-title":"Relative, quantitative effects of acceptors in the reaction of Leuconostoc mesenteroides B-512F dextransucrase","volume":"121","author":"Robyt","year":"1983","journal-title":"Carbohydr. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"383","DOI":"10.13050\/foodengprog.2017.21.4.383","article-title":"Oligosaccharide production by Leuconostoc lactis CCK940 which has glucansucrase activity","volume":"21","author":"Lee","year":"2017","journal-title":"Food Eng. Prog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.aca.2009.06.015","article-title":"Experimental design in chemistry: A tutorial","volume":"652","author":"Leardi","year":"2009","journal-title":"Anal. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3707","DOI":"10.1007\/s13197-017-2835-x","article-title":"Enzymatic pectic oligosaccharides (POS) production from sugar beet pulp using response surface methodology","volume":"54","author":"Babbar","year":"2017","journal-title":"J. Food Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3136\/fstr.18.195","article-title":"Immunomodulatory effects of xylooligosaccharides","volume":"18","author":"Chen","year":"2012","journal-title":"Food Sci. Technol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1021\/jf405633n","article-title":"Immunomodulatory effects of alginate oligosaccharides on murine macrophage RAW264.7 cells and their structure-activity relationships","volume":"62","author":"Xu","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1016\/j.biortech.2007.07.027","article-title":"Enhanced production of exocellular glucansucrase from Leuconostoc dextranicum NRRL B-1146 using response surface method","volume":"99","author":"Majumder","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_17","unstructured":"Lee, S.H., Jang, J.K., and Park, Y.S. (2018, January 27\u201329). Optimization of oligosaccharide production using response surface methodology and its immunostimulating effect on RAW264.7 macrophage cell. Proceedings of the 2018 KoSFoST International Symposium and Annual Meeting, Busan, Korea."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/0753-3322(94)90005-1","article-title":"Dossier cytokines and macrophages","volume":"48","author":"Cavaillon","year":"1994","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jff.2016.06.002","article-title":"Structural elucidation, chain conformation and immuno-modulatory activity of glucogalactomannan from cultured Cordyceps sinensis fungus UM01","volume":"25","author":"Cheong","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/ni1001-907","article-title":"Nitric oxide and the immune response","volume":"2","author":"Bogdan","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1073\/pnas.012511599","article-title":"Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: Regulatory role in the innate immune response","volume":"99","author":"Mitchell","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1089\/jmf.2016.0030","article-title":"Inhibition of TNF-\u03b1, IL-1\u03b1, and IL-1\u03b2 by pretreatment of human monocyte-derived macrophages with menaquinone-7 and cell activation with TLR agonists in vitro","volume":"19","author":"Pan","year":"2016","journal-title":"J. Med. Food"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.intimp.2009.12.011","article-title":"Purification, characterization and immunostimulating activity of water-soluble polysaccharide isolated from Capsosiphon fulvescens","volume":"10","author":"Na","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.intimp.2013.06.013","article-title":"Immunostimulatory effects and characterization of a glycoprotein fraction from rice bran","volume":"17","author":"Park","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0165-2478(96)02669-7","article-title":"The function of the soluble IL-6 receptor in vivo","volume":"54","author":"Peters","year":"1996","journal-title":"Immunol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/333664a0","article-title":"Vascular endothelial cells synthesize nitric oxide from L-arginine","volume":"333","author":"Palmer","year":"1988","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0024-3205(01)01154-7","article-title":"Camptothecin suppresses nitric oxide biosynthesis in RAW264.7 macrophages","volume":"69","author":"Chiou","year":"2001","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0306-3623(01)00086-6","article-title":"Inhibitory effect of ethyl acetate fraction from Cudrania tricuspidata on the expression of nitric oxide synthase gene in RAW264.7 macrophages stimulated with interferon-\u03b3 and lipopolysaccharide","volume":"35","author":"Seo","year":"2001","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_29","first-page":"394","article-title":"Immune-stimulating effects of Polygonum aviculare L. extract on macrophages","volume":"57","author":"Jeon","year":"2013","journal-title":"Yakhak Hoeji"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/9\/2118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:20:32Z","timestamp":1760196032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/9\/2118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,23]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["molecules23092118"],"URL":"https:\/\/doi.org\/10.3390\/molecules23092118","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,23]]}}}