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1 Research Trend on the Immune modulation of Lactic Acid Bacteria and Milkderived Peptide Cheol-Hyun Kim Department of Animal Resource & Science, Dankook university,,.. (Lactic acid bacteria) gram-positive lactic acid (Mugitani and Furue, 1987). probiotics (Salminen et al., 1999), Probiotics,,, (Salminen et al., 2011), (Spanhaak et al., 1998), Table 1. Distribution of the microbiota in the digestive system (Aureli et al., 2011) Site Bacterial cells per gram of intestinal contents Notes Stomach, duodenum <10 3 Lactobacilli, Streptococci HCl, peristalsis and bile inhibit the adhesion of bacteria and prevent colonization Fasting, ileus, distal ileum Lack of information: likely activity of fermentation of carbohydrates Large intestine (prevalence of anaerobe) Body location of most microbiota activities *Corresponding author: Chorl-Hyun Kim, Department of Animal Resource & Science, Dankook University, Cheonan , Korea. Tel: , Fax: , hichkim@dankook.ac.kr 2012, 12 (Vol.1, No.2) 37

(Blocksma et al., 1979). lactic acid, acetic acid nisin bacteriocin,, (Irritable bowel syndrome, IBS), (Lactose intolerance),, (Bang et al., 2012; Alander et al., 1999; Axselsson et al.

2 (Blocksma et al., 1979). lactic acid, acetic acid nisin bacteriocin,, (Irritable bowel syndrome, IBS), (Lactose intolerance),, (Bang et al., 2012; Alander et al., 1999; Axselsson et al., 1989; Seo et al., 2010; Vrese et al., 2001)., (FitzGerald et al., 2004), (Williams et al., 2002)., allergy,., (Korhonen and Pihlanto, 2006)., (Nagpal et al., 2011). (non-specific immunity),. macrophage, neutrophil, basophil, eosinophil, NKcell, dendritic cell(dc) mast cell., (specific immunity). B (B lympocyte) T (T lympocyte), B T, T NK-cell lymphokine (Kim, 2009). Fig. 1. Integrated human immune system (Turvey and Broide, 2010) NK-cell (Moretta et al., 2002; O Connor et al., 2005), NK-cell 10% CD56 positive CD3 negative cell (Cooper et al., 2001)., NK-cell IFN-, cytotoxic T-cell (Robertson, 2002; Bryceson et al., 2006; Marcenaro et al., 2006), 38

, 2012) NK-cell (Terme et al., 2008). Lympokine-activated killer(lak) cell, CTL, NK-cell (Kagi et al.

, cytokine (Matusuzaki et al., 1988; Matusuzaki, 1998). polysaccharide (Cross et al., 2001). immunocompetent cell.

3 Fig. 2. IL-1 family cytokine-induced cytokine production provides a mechanism for a rapid innate response (Guo et al., 2012) NK-cell (Terme et al., 2008). Lympokine-activated killer(lak) cell, CTL, NK-cell (Kagi et al., 1994; Lowin et al., 1994; Sayers et al., 1998)., (Hove et al., 1999; Kaila and James, 2000; Kent and Neil, 2000)., cytokine (Matusuzaki et al., 1988; Matusuzaki, 1998). polysaccharide (Cross et al., 2001). immunocompetent cell., IFN-, TNF-a, IL-12 Fig. 3. The fate of LAB and antigens in the intestinal tract (Wells and Mercenier, 2008) Fig. 4. Mechanisms of host defence against and tolerance to intestinal microorganisms (Bron et al., 2011) 2012, 12 (Vol.1, No.2) 39

4 (Perdigon et al., 1999), NK-cell cytokine NK-cell (Cheon et al., 2011; Kosaka et al., 2012), NK-cell.,, L. reuteri, L. johnsonii/gasseri, L. Table 2. Immune responses elicited by the exopolysaccharides(eps) synthesised by bacteria present in foods (Hidalgo- Cantabrana et al., 2012) Producing bacterium Bacterial strain characteristic EPS characteristic Immune response Study model Lactococcus lactis subsp. cremoris KVS20 HePS, acid (2.2 % PO 4 ), high M w Stimulation In vitro mice spleen macrophages Lactobacillus delbrueckii subsp. bulgaricus OLL-1073R-1 HePS, acid fraction Strong stimulation (0.1 % PO 4 ), high M w In vitro mice spleen cells and PPL Leuconostoc mesenteroides Lactobacillus kefiranofaciens Bifidobacterium longum Lactobacillus casei Commercial dextran HePS, neutral fraction HoPS, -glucan (dextran) HoPS, P-dextran (1.7 % PO 4 ) Weak stimulation Weak stimulation Strong stimulation In vitro mice spleen macrophages ATCC HePS (kefiran) Stimulation In vivo mice model BCRC Unknown Mild modulator YIT 9019 (Shirota, parental) KO-mutants HePS, high M w + low M W HePS (low M W?) Suppression In vitro macrophage mice J77A.1 cell line In vitro mice spleen cells and mice Lactobacillus rhamnosus Bifidobacterium animalis subsp.lactis Bifidobacterium breve ATCC9595 (parental) RW-9595M(derivative) A1 (parental, food origin) A1dOx (bile adapted) A1dOxR (bile adapted, ropy) UCC 2003 (parental EPS?) UCC2003-EPS HePS ( rham) HePS ( rham), high MW HePS, low Mw HePS, low Mw HePS( rham), low Mw + high Mw Stimulation Stimulation In vitro mice macrophages In vitro human PBMC HePS No production Suppression In vivo mice model Pediococcus parvulus 2.6R (ropy, parental) HoPS, 2-substituted (1 3)- -glucan Suppression In vitro polarised human macrophages Propionibacterium freudenreichii CB1 (=TL34) (parental) CB1-KO (gtf inactivated) HoPS, 2-substituted (1 3)- -glucan No production Stimulation In vitro human PBMC *HePS heteropolysaccharide, HoPS homopolysaccharide, Rham rhamnose, Gal galactose, Mw molecular weight, PPL Payer s patches lymphocytes, PBMC peripheral blood mononuclear cells 40

Fig. 5. Mechanistic view of probiotic actions by lactobacilli (Lebeer et. al., 2008) murinus/animalis, L. reuteri 100-23 L.

, 2012), Lactobacillus rhamnosus strain HN001 Salmonella typhimurium Balc/C,, (Gill et al., 2001). L. plantarum 2142 Hsp70 IL-8 TNF-a (Paszti-Gere et al., 2012)., TNF-a, NO (Lin et al.

5 Fig. 5. Mechanistic view of probiotic actions by lactobacilli (Lebeer et. al., 2008) murinus/animalis, L. reuteri L. gasseri , atrophy marker(antrogin-1, MuRF1, LC3, Cathepsin L), interleukin-6, monocyte chemoattractant protein-1, interleukin-4.(bindels et al., 2012), Lactobacillus rhamnosus strain HN001 Salmonella typhimurium Balc/C,, (Gill et al., 2001). L. plantarum 2142 Hsp70 IL-8 TNF-a (Paszti-Gere et al., 2012)., TNF-a, NO (Lin et al., 2007) IL-12 IFN- (Kato et al., 1999; Matsuzaki and Chin, 2000; Sashihara et al., 2008). peptidoglycan. casein whey protein,,.,,,, ACE (Korhonen and Pihlanto, 2006)., peptide (Saito et al., 2000; FitzGerald and Murray, 2006; Korhonen and Pihlanto-Leppälä, 2004; Sienkiewicz-Szlapka et al., 2009b), Casein peptide peptide, peptide 2 20 (Meisel and FitzGerald, 2000). peptide (Matar et al., 1997), (Laffineur et al., 1996) (Moineau and Goulet, 1991), L. helveticus (Yamamoto et al., 1994 and 1999; Maeno et al., 1996). casein whey protein, Fig. 6. Functionality of milk-derived bioactive peptides and their potential health targets (Korhonen, 2009) 2012, 12 (Vol.1, No.2) 41

6 Table 3. Milk-derived bioactive peptides in commercially available functional foods and ingredients (Mills et al., 2011) Bioactive peptide Health claim Product type Brand name Manufacturer VPP, IPP from casein and -casein VPP, IPP from casein and -casein Whey peptides Reduction of blood pressure Reduction of blood pressure Reduction of blood pressure Sour milk Calpis Calpis Co., Japan Fermented milk, calcium enriched Hydrolysed whey protein isolate Evolus BioZate Valio, Finland Davisco, USA Casein-derived dodecapeptide FFVAPF- PEVFGK Reduction of blood pressure Ingredient C12 Peption DMV, The Netherlands Casein-derived dodecapeptide FFVAPF- PEVFGK Reduction of blood pressure Soft drink Casein DP Peptio Drink Kanebo, Japan Glycomacropeptide -casein f ( ) s1 -casein f (91-100) YLGYLEQLLR Anticariogenic, antimicrobial, antithrombic Reduce stress Whey protein isolate Milk drink, confectionary BioPURE-GMP CSPHP ProDiet F200 Davisco, USA Ingredia, France Casein phosphopeptide Helps mineral absorption Ingredient Capolac Arla Foods, Denmark Casein phosphopeptide Helps mineral absorption Soft drink Tekkotsu Inryou Suntory, Japan Casein phosphopeptide Helps mineral absorption Soft drink Kotsu Kotsu Calcium Asahi, Japan Casein phosphopeptide Helps mineral absorption Ingredient CE90CPP DMV, The Netherlands Glutamine-rich peptides Immunomodulatory Dry milk protein hydrolysate Glutamine Peptide DMV, The Netherlands s1-casein f (1-6) RPKHPI, f (1-7) RPKHPIK, f (1-9) RPKHPIKHQ, Reduction of blood pressure Fermented low fat hard cheese Festivo MTT AgrifoodResearch, Finland Milk-derived peptide Boost energy, improve sleep quality Ingredient Cysteine Peptide DMV, The Netherlands Casein-derived peptide Improves athletic performance and muscle recovery Ingredient PeptoPro DSM, The Netherlands Whey-derived peptide Aids relaxation and sleep Ingredient Vivinal Alpha Borcula Domo Ingredients (BDI), The Netherlands Casein phosphopeptides Anticariogenic Chewing gum Recaldent Cadbury Enterprises Milk-derived peptides Reduction of blood pressure Margarine Evolus Double Effect Spread Valio, Finland 42

7 , (Cross and Gill, 2000).,,,,, NK-cell (Gauthier et al., 2006). T B, IFN- mitogen-induced T-cell (Cross and Gill, 1999)., microfiltering whey protein in vitro (Mercier et al., 2004). immunoglobulin IgG, cytokine TNF-a, IL-1, -2, -6 transforming growth factor(tgf), insulin-like growth factor (IGF-I, II) epidermal growth factor(egf)., transforming growth factor- (TGF- ), cytokine. 10mg/mL RAW 264.7, heme oxygenase-1 TNF-a, IL-1, IL-6 NO (Yang et al., 2012). -casein (Meisel and Schlimme, 2009), a-lactalbumin, -casein (Sfaxi et al., 2012).,.,, cytokine.,.,,,,,,. GRAS(generally recognise as safe). (,, ph). in vivo.. 1. Alander, M., Satokari, R., Korpela, R., Saxelin, M., Vilpponen-Salmela, T. and von Wright. A. (1999) Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl. Environ. Microbiol. 65, Aureli, P., Capurso, L., Castellazzi, A. M., Cherici, M., Giovannini, M., Morelli, L., Poli, A., Pregliasco, F., Salvini, F., and Zuccotti, G. V. (2011) Probiotics and Health: An Evidence- Based Review. Pharmacol. Res. 63, Axelsson, L. T., Chung, T. C., Dobrogosz, W. G. and Lindgren, S. E. (1989) Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microb. Ecol. Health Dis. 2, Bang, J. H., Shin, H. J., Choi, H. J., Kim, D. W., Ahn, C. S., Jeong, Y. K., and Joo, W. H. (2012) Probiotic Potential of Lactobacillus isolates. J. Life Sci. 22, Bindels, L. B., Beck, R., Schakman, O., Martin, J. C., De backer, F., Sohet, F. M., Dewulf, E. M., Pachikian, B. D., Neyrinck, A. M., Thissen, J. P., Verrax, J., Calderon, P. B., Pot, B., Grangette, C., Cani, P. D., Scott, K. P., and Delzenne, N. M. (2012) Restoring Specific Lactobacilli Levels Decreases Inflammation and Muscle Atrophy Markers in an Acute Leukemia Mouse Model. PLoS ONE. 7, e , 12 (Vol.1, No.2) 43

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untitled 3. 농업환경연구과 과제구분 기본연구 수행시기 전반기 연구과제 및 세부과제 수행 기간 소 속 책임자 농가에 적합한 부식성곤충 대량 사육기술 개발 12~ 13 농업환경연구과 곤충팀 이영혜 1) 부식성 곤충 먹이 제조 기술 개발 12~ 13 농업환경연구과 곤충팀 이영혜 색인용어 부식성곤충, 장수풍뎅이, 계통, 먹이제조 ABSTRACT In first check,