Korean Journal of Agricultural Science (농업과학연구)

Institute of Agricultural Science, CNU (충남대학교 농업과학연구소)
권호 표지
DOI QR코드

DOI QR Code

Characterization of lactoferrin hydrolysates on inflammatory cytokine expression in Raw264.7 macrophages

  • Son, Ji Yoon (Department of Animal Biosystem Science, College of Agriculture and Life Sciences, Chungnam National University) ;
  • Park, Young W. (Agricultural Research Station, Fort Valley State University, Fort Valley, GA 31030, USA and Department of Food Science and Technology, University of Georgia) ;
  • Renchinkhand, Gereltuya (Department of Animal Biosystem Science, College of Agriculture and Life Sciences, Chungnam National University) ;
  • Paik, Seung-Hee (Division of Food Service Industry, Yonam College) ;
  • Nam, Myoung Soo (Department of Animal Biosystem Science, College of Agriculture and Life Sciences, Chungnam National University)
  • Received : 2018.04.10
  • Accepted : 2018.07.03
  • Published : 2018.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Lactoferrin is an iron-binding glycoprotein which is present in colostrum, milk, and other body secretions. Lactoferrin activities are associated with inflammatory and immune responses. The aim of this study was to investigate the effect of lactoferrin hydrolysates (LH) on the production of immunomodulatory factors such as inflammatory related cytokines (tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, interleukin (IL)-6, and interleukin (IL)-13) in Raw264.7 cells, which originated from murine macrophages. The results show that the Raw264.7 cells cultured in 3 types (whole, and above and below 10 kDa) of lactoferrin hydrolysates (LH) did not show any cytotoxicity in the cells. $TNF-{\alpha}$ decreased dose-dependently to 1,500 - 2,000 ng/mL by treatment with the 3 types of LH at 1, 50, $100{\mu}g/mL$, whereas the positive control, lipopolysaccharide (LPS), and negative control produced 2,450 and 1,000 ng/mL of $TNF-{\alpha}$, respectively, in the Raw264.7 cells. The treatment with the 3 types of LH (whole and above and below 10 kDa) at $50{\mu}g/mL$ produced about 20 - 28 ng/mL of $IL-1{\beta}$ at 3, 6, and 9 h, respectively, while the negative control produced 7 ng/mL, and LPS as the positive control produced 48 - 60 ng/mL. $TNF-{\alpha}$ and IL-6 expression was decreased dose-dependently by the 3 types of LH. The mRNA levels of IL-13 were slightly increased dose-dependently by the whole and above 10 kDa LH, but decreased dose-dependently by the below 10 kDa LH in the Raw264.7 cells. The results show that LH had immunomodulating effects on cytokine production in anti- and pro-inflammatory reactions as well as anti-allergic reactions.

Keywords

References

  1. Aisen P, Leibman A. 1972. Lactoferrin and transferrin: A comparative study. BBA-Protein Structure 257:314-323. https://doi.org/10.1016/0005-2795(72)90283-8
  2. Arai KI, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T. 1990. Cytokines: Coordinators of immune and inflammatory responses. Annual Review Biochemistry 59:783-836. doi:10.1146/annurev.bi.59.070190.004031
  3. Baker E, Baker H. 2005. Lactoferrin. Cellular and Molecular Life Sciences 62:2531-2539. https://doi.org/10.1007/s00018-005-5368-9
  4. Chung SH, Kang HB, Kim JW, Yoon SS, Nam MS. 2012. The biological effects of bovine lactoferrin on inflammatory cytokine expression in the PMA stimulated cells. Korean Journal for Food Science of Animal Resources 32:364-368. https://doi.org/10.5851/kosfa.2012.32.3.364
  5. Clare DA, Swaisgood HE. 2000. Bioactive milk peptides: A prospectus. Journal of Dairy Science 83:1187-1195. https://doi.org/10.3168/jds.S0022-0302(00)74983-6
  6. Crouch SP, Slater KJ, Fletcher J. 1992. Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 80:235-240.
  7. FitzGerald RJ, Meisel H. 2003. Milk protein hydrolysates and bioactive peptides. In Advances in Dairy Chemistry edited by Fox PF, McSweeney, PLH. 3rd Eds. pp. 657-698. Kluwer Academic/Plenum Publishers, NY, USA.
  8. Gonzalez-Chavez SA, Arevalo-Gallegos S, Rascon-Cruz Q. 2008. Lactoferrin: Structure, function and applications. International Journal of Antimicrobial Agents 33:301.e1-8. doi:10.1016/j.ijantimicag.07.020.
  9. Haversen L, Ohlsson BG, Hahn-Zoric M, Hanson LA, Mattsby-Baltzer I. 2002. Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-${\kappa}$-b. Cell Immunology 220:83-95. https://doi.org/10.1016/S0008-8749(03)00006-6
  10. Iafisco M, Foggia MD, Bonora S, Prat M, Roveri N. 2011. Adsorption and spectroscopic characterization of lactoferrin on hydroxyapatite nanocrystals. Dalton Transactions 40:820-827. https://doi.org/10.1039/C0DT00714E
  11. Iigo M, Alexander DB, Long N, Xu J, Fukamachi K, Futakuchi M, Takase M, Tsuda H. 2009. Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie 91:86-101. https://doi.org/10.1016/j.biochi.2008.06.012
  12. Kitts DD, Weiler K. 2003. Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Current Pharmaceutical Design 9:1309-1323. https://doi.org/10.2174/1381612033454883
  13. Kong CS. 2014. Anti-inflammatory activity of the solvent-partitioned fractions from Spergularia marina in LPS-stimulated RAW 264.7 cells. Preventive Nutrition and Food Science 19:261-267. https://doi.org/10.3746/pnf.2014.19.4.261
  14. Korhonen H, Pihlanto A. 2007. Bioactive peptides from food proteins. Handbook of food products manufacturing. In edited by Hui YH. pp. 5-37. John Wiley &Sons, Inc., California, USA.
  15. Kruzel ML, Harari Y, Mailman D, Actor JK, Zimecki M. 2002. Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice. Clinical & Experimental Immunology 130: 25-31. https://doi.org/10.1046/j.1365-2249.2002.01956.x
  16. Legrand D, Elass E, Carpentier M, Mazurier J. 2005. Lactoferrin: A modulator of immune and inflammatory responses. Cellular and Molecular Life Sciences 62: 2549-2559. https://doi.org/10.1007/s00018-005-5370-2
  17. LI G, Le G, Shi Y, Shrestha S. 2004. Angiotensin 1-converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects. Nutrition Research 24:469-486. https://doi.org/10.1016/S0271-5317(04)00058-2
  18. Parhi P, Mohanty C, Sahoo SK. 2012. Nanotechnology-based combinational drug delivery: An emerging approach for cancer therapy. Drug Discovery Today 17-18:1044-1052.
  19. Park YW, Nam MS. 2015. Bioactive peptides in milk and dairy products: Review. Korean Journal for Food Science of Animal Resources 35:831-840. https://doi.org/10.5851/kosfa.2015.35.6.831
  20. Prgomet C, Peters S, Pfaffl MW. 2006. Influence of bovine lactoferrin and lactoferricin on cytokine expression in LPS-treated cultivated bovine blood cells. Journal of the Science of Food and Agriculture 86:640-647. https://doi.org/10.1002/jsfa.2377
  21. Schagger H, von Jagow G. 1987. Tricine-sodium dodecyl sulfate polyacrylamide gel electrophoresis for the separation of proteins in the range from 1-100 kD. Analytical Biochemistry 166:368-379. https://doi.org/10.1016/0003-2697(87)90587-2
  22. Sindayikengera S, Xia W. 2006. Nutrition evaluation of casein and whey proteins and their hydrolysates from Protamex. Journal of Zhejiang University Science B 7:90-98. https://doi.org/10.1631/jzus.2006.B0090
  23. Stancius N, Hintoiu A, Stanciu S, Rapeanu G. 2010. Thermal treatment can modify the susceptibility of whey protein concentrate to enzymatic hydrolysis. Innovative Romanian Food Biotechnology 7:30-36.
  24. Storcksdieck GBS, Hurrell RE. 2007. Iron-binding properties, amino acid composition, and structure of muscle tissue peptides from in vitro digestion of different meat sources. Journal of Food Science 72:S019-S029.
  25. Yamaguchi M, Matsuura M, Kobayashi K, Sasaki H, Yajima T, Kuwata T. 2001. Lactoferrin protects against development of hepatitis caused by sensitization of kupffer cells by lipopolysaccharide. Clinical and Diagnostic Laboratory Immunology 8:1234-1239.