Skip to main content
Log in

Bursopentin (BP5) from chicken bursa of fabricius attenuates the immune function of dendritic cells

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Bursopentine (BP5), a novel pentapeptide isolated from chicken bursa of fabricius, has been proved to have immunomodulatory effects on B and T lymphocytes, anti-oxidative stress on macrophages, and antiproliferation on tumor cells. However, the effects of BP5 on the immune function exhibited by dendritic cells (DCs), which are regarded as a major target for immunomodulators, remain unknown. In this study, we examined the effects of BP5 on the activation and maturation of murine bone marrow-derived DCs. Our results showed that BP5 significantly suppressed the secretion of lipopolysaccharide (LPS)-induced pro-inflammatory (TNF-α, IL-1β, IL-6 and IL-12p70) and anti-inflammatory (IL-10) cytokines by DCs, and this impact was not due to its cytotoxicity. Besides, BP5 reversed the morphological changes and attenuated the expression of phenotypic markers (MHC II, CD40, CD80 and CD86 molecules) in LPS-induced DCs. Furthermore, BP5 restored the decreased FITC-dextran uptake in LPS-treated DCs, arrested the LPS-induced migration of DCs and abrogated the promoting ability of LPS-induced DCs for allogeneic T cell proliferation. These findings show a new immunopharmacological capability of BP5 and provide a novel approach in the prevention and therapy of chronic inflammation and autoimmunity via abolishing the immune function of DCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Ahn SC, Kim GY, Kim JH, Baik SW, Han MK, Lee HJ, Moon DO, Lee CM, Kang JH, Kim BH, Oh YH, Park YM (2004) Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and NF-kappaB. Biochem Biophys Res Commun 313(1):148–155

    Article  CAS  PubMed  Google Scholar 

  • Akira S, Takeda K (2004) Toll-like receptor signalling. Nature Rev Immunol 4(7):499–511. doi:10.1038/nri1391

    Article  CAS  Google Scholar 

  • Alvarez D, Vollmann EH, von Andrian UH (2008) Mechanisms and consequences of dendritic cell migration. Immunity 29(3):325–342. doi:10.1016/j.immuni.2008.08.006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bakri Y, Sarrazin S, Mayer UP, Tillmanns S, Nerlov C, Boned A, Sieweke MH (2005) Balance of MafB and PU1 specifies alternative macrophage or dendritic cell fate. Blood 105(7):2707–2716. doi:10.1182/blood-2004-04-1448

    Article  CAS  PubMed  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252. doi:10.1038/32588

    Article  CAS  PubMed  Google Scholar 

  • Brand A, Gilmour DG, Goldstein G (1976) Lymphocyte-differentiating hormone of bursa of fabricius. Science 193(4250):319–321

    Article  CAS  PubMed  Google Scholar 

  • Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 174(6):3237–3246

    Article  PubMed  Google Scholar 

  • Ding X, Yang W, Shi X, Du P, Su L, Qin Z, Chen J, Deng H (2011) TNF receptor 1 mediates dendritic cell maturation and CD8 T cell response through two distinct mechanisms. J Immunol 187(3):1184–1191. doi:10.4049/jimmunol.1002902

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Efron P, Moldawer LL (2003) Sepsis and the dendritic cell. Shock 20(5):386–401. doi:10.1097/01.SHK.0000092698.10326.6f

    Article  PubMed  Google Scholar 

  • Eriksson U, Kurrer MO, Sonderegger I, Iezzi G, Tafuri A, Hunziker L, Suzuki S, Bachmaier K, Bingisser RM, Penninger JM, Kopf M (2003) Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis. J Exp Med 197(3):323–331

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Feng X, Liu T, Wang F, Cao R, Zhou B, Zhang Y, Mao X, Chen P, Zhang H (2011) Isolation, antiproliferation on tumor cell and immunomodulatory activity of BSP-I, a novel bursal peptide from chicken humoral immune system. Peptides 32(6):1103–1109. doi:10.1016/j.peptides.2011.04.020

    Article  CAS  PubMed  Google Scholar 

  • Feng XL, Liu QT, Cao RB, Zhou B, de Li Y, Zhang YP, Liu K, Liu XD, Wei JC, Qiu YF, Li XF, Ma ZY, Chen PY (2012a) Gene expression profiling of hybridoma cells after bursal-derived bioactive factor BP5 treatment. Amino Acids 43(6):2443–2456. doi:10.1007/s00726-012-1323-x

    Article  CAS  PubMed  Google Scholar 

  • Feng XL, Liu QT, Cao RB, Zhou B, Wang FQ, Deng WL, Qiu YF, Zhang Y, Ishag H, Ma ZY, Zheng QS, Chen PY (2012b) A bursal pentapeptide (BPP-I), a novel bursal-derived peptide, exhibits antiproliferation of tumor cell and immunomodulator activity. Amino Acids 42(6):2215–2222. doi:10.1007/s00726-011-0961-8

    Article  CAS  PubMed  Google Scholar 

  • Finkelman FD, Lees A, Birnbaum R, Gause WC, Morris SC (1996) Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J Immunol 157(4):1406–1414

    CAS  PubMed  Google Scholar 

  • Forster R, Davalos-Misslitz AC, Rot A (2008) CCR7 and its ligands: balancing immunity and tolerance. Nature Rev Immunol 8(5):362–371. doi:10.1038/nri2297

    Article  Google Scholar 

  • Green CE, Liu T, Montel V, Hsiao G, Lester RD, Subramaniam S, Gonias SL, Klemke RL (2009) Chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization. PLoS One 4(8):e6713. doi:10.1371/journal.pone.0006713

    Article  PubMed Central  PubMed  Google Scholar 

  • Higgins SC, Lavelle EC, McCann C, Keogh B, McNeela E, Byrne P, O’Gorman B, Jarnicki A, McGuirk P, Mills KH (2003) Toll-like receptor 4-mediated innate IL-10 activates antigen-specific regulatory T cells and confers resistance to Bordetella pertussis by inhibiting inflammatory pathology. J Immunol 171(6):3119–3127

    Article  CAS  PubMed  Google Scholar 

  • Huang RY, Yu YL, Cheng WC, OuYang CN, Fu E, Chu CL (2010) Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol 184(12):6815–6821. doi:10.4049/jimmunol.0903991

    Article  CAS  PubMed  Google Scholar 

  • Humrich JY, Thumann P, Greiner S, Humrich JH, Averbeck M, Schwank C, Kampgen E, Schuler G, Jenne L (2007) Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells. Eur J Immunol 37(4):954–965. doi:10.1002/eji.200636230

    Article  CAS  PubMed  Google Scholar 

  • Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM (1992) Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 176(6):1693–1702

    Article  CAS  PubMed  Google Scholar 

  • Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327(5963):291–295. doi:10.1126/science.1183021

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim JY, Kang JS, Kim HM, Kim YK, Lee HK, Song S, Hong JT, Kim Y, Han SB (2009) Inhibition of phenotypic and functional maturation of dendritic cells by manassantin a. J Pharmacol Sci 109(4):583–592

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, Kang JS, Kim HM, Ryu HS, Kim HS, Lee HK, Kim YJ, Hong JT, Kim Y, Han SB (2010) Inhibition of bone marrow-derived dendritic cell maturation by glabridin. Int Immunopharmacol 10(10):1185–1193. doi:10.1016/j.intimp.2010.06.025

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi M, Azuma E, Ido M, Hirayama M, Jiang Q, Iwamoto S, Kumamoto T, Yamamoto H, Sakurai M, Komada Y (2001) A pivotal role of Rho GTPase in the regulation of morphology and function of dendritic cells. J Immunol 167(7):3585–3591

    Article  CAS  PubMed  Google Scholar 

  • Lassila O, Lambris JD, Gisler RH (1989) A role for Lys-His-Gly-NH2 in avian and murine B cell development. Cell Immunol 122(2):319–328

    Article  CAS  PubMed  Google Scholar 

  • Lee JS, Kim SG, Kim HK, Lee TH, Jeong YI, Lee CM, Yoon MS, Na YJ, Suh DS, Park NC, Choi IH, Kim GY, Choi YH, Chung HY, Park YM (2007) Silibinin polarizes Th1/Th2 immune responses through the inhibition of immunostimulatory function of dendritic cells. J Cell Physiol 210(2):385–397. doi:10.1002/jcp.20852

    Article  CAS  PubMed  Google Scholar 

  • Levings MK, Sangregorio R, Roncarolo MG (2001) Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 193(11):1295–1302

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li JW, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325(5937):161–165. doi:10.1126/science.1168243

    Article  PubMed  Google Scholar 

  • Li DY, Geng ZR, Zhu HF, Wang C, Miao DN, Chen PY (2011) Immunomodulatory activities of a new pentapeptide (Bursopentin) from the chicken bursa of Fabricius. Amino Acids 40(2):505–515. doi:10.1007/s00726-010-0663-7

    Article  CAS  PubMed  Google Scholar 

  • Li DY, Xue MY, Geng ZR, Chen PY (2012) The suppressive effects of Bursopentine (BP5) on oxidative stress and NF-kB activation in lipopolysaccharide-activated murine peritoneal macrophages. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 29(1–2):9–20. doi:10.1159/000337581

    Article  Google Scholar 

  • Lien E, Chow JC, Hawkins LD, McGuinness PD, Miyake K, Espevik T, Gusovsky F, Golenbock DT (2001) A novel synthetic acyclic lipid A-like agonist activates cells via the lipopolysaccharide/toll-like receptor 4 signaling pathway. J Biol Chem 276(3):1873–1880. doi:10.1074/jbc.M009040200

    Article  CAS  PubMed  Google Scholar 

  • Lin MK, Yu YL, Chen KC, Chang WT, Lee MS, Yang MJ, Cheng HC, Liu CH, Chen DzC, Chu CL (2011) Kaempferol from semen cuscutae attenuates the immune function of dendritic cells. Immunobiology 216(10):1103–1109. doi:10.1016/j.imbio.2011.05.002

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, Chen T, Chen G, Shu X, Sun A, Ma P, Lu L, Cao X (2007) Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways. Mol Immunol 44(10):2686–2696. doi:10.1016/j.molimm.2006.12.003

    Article  CAS  PubMed  Google Scholar 

  • Lu L, McCaslin D, Starzl TE, Thomson AW (1995) Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2-) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes. Transplantation 60(12):1539–1545

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lutz MB, Assmann CU, Girolomoni G, Ricciardi-Castagnoli P (1996) Different cytokines regulate antigen uptake and presentation of a precursor dendritic cell line. Eur J Immunol 26(3):586–594. doi:10.1002/eji.1830260313

    Article  CAS  PubMed  Google Scholar 

  • Maloy KJ, Powrie F (2001) Regulatory T cells in the control of immune pathology. Nature Immunol 2(9):816–822. doi:10.1038/ni0901-816

    Article  CAS  Google Scholar 

  • Manicassamy S, Pulendran B (2009) Modulation of adaptive immunity with Toll-like receptors. Semin Immunol 21(4):185–193. doi:10.1016/j.smim.2009.05.005

    Article  CAS  PubMed  Google Scholar 

  • Masteller EL, Lee KP, Carlson LM, Thompson CB (1995) Expression of sialyl Lewis(x) and Lewis(x) defines distinct stages of chicken B cell maturation. J Immunol 155(12):5550–5556

    CAS  PubMed  Google Scholar 

  • Means TK, Jones BW, Schromm AB, Shurtleff BA, Smith JA, Keane J, Golenbock DT, Vogel SN, Fenton MJ (2001) Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-induced macrophage responses. J Immunol 166(6):4074–4082

    Article  CAS  PubMed  Google Scholar 

  • Michiels A, Tuyaerts S, Bonehill A, Corthals J, Breckpot K, Heirman C, Van Meirvenne S, Dullaers M, Allard S, Brasseur F, van der Bruggen P, Thielemans K (2005) Electroporation of immature and mature dendritic cells: implications for dendritic cell-based vaccines. Gene Ther 12(9):772–782. doi:10.1038/sj.gt.3302471

    Article  CAS  PubMed  Google Scholar 

  • Moore KJ, Andersson LP, Ingalls RR, Monks BG, Li R, Arnaout MA, Golenbock DT, Freeman MW (2000) Divergent response to LPS and bacteria in CD14-deficient murine macrophages. J Immunol 165(8):4272–4280

    Article  CAS  PubMed  Google Scholar 

  • Mueller AP, Wolfe HR, Meyer RK, Aspinall RL (1962) Further studies on the role of the bursa of Fabricius in antibody production. J Immunol 88:354–360

    CAS  PubMed  Google Scholar 

  • Nguyen LT, Radhakrishnan S, Ciric B, Tamada K, Shin T, Pardoll DM, Chen L, Rodriguez M, Pease LR (2002) Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells. J Exp Med 196(10):1393–1398

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • O’Neill LA, Bowie AG (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nature Rev Immunol 7(5):353–364. doi:10.1038/nri2079

    Article  Google Scholar 

  • Pashenkov M, Teleshova N, Kouwenhoven M, Kostulas V, Huang YM, Soderstrom M, Link H (2002) Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple sclerosis and acute optic neuritis. Clin Exp Immunol 127(3):519–526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Piccirillo CA, Shevach EM (2001) Cutting edge: control of CD8+T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol 167(3):1137–1140

    Article  CAS  PubMed  Google Scholar 

  • Prechtel AT, Turza NM, Kobelt DJ, Eisemann JI, Coffin RS, McGrath Y, Hacker C, Ju X, Zenke M, Steinkasserer A (2005) Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration. J Gen Virol 86(Pt 6):1645–1657. doi:10.1099/vir.0.80852-0

    Article  CAS  PubMed  Google Scholar 

  • Reis e Sousa C (2006) Dendritic cells in a mature age. Nature Rev Immunol 6(6):476–483. doi:10.1038/nri1845

    Article  CAS  Google Scholar 

  • Ritter U, Meissner A, Ott J, Korner H (2003) Analysis of the maturation process of dendritic cells deficient for TNF and lymphotoxin-alpha reveals an essential role for TNF. J Leukoc Biol 74(2):216–222

    Article  CAS  PubMed  Google Scholar 

  • Santiago-Schwarz F (2004) Dendritic cells: friend or foe in autoimmunity? Rheum Dis Clin N Am 30(1):115–134. doi:10.1016/S0889-857X(03)00108-X

    Article  Google Scholar 

  • Seitz HM, Matsushima GK (2010) Dendritic cells in systemic lupus erythematosus. Int Rev Immunol 29(2):184–209. doi:10.3109/08830181003602507

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shi JQ, Chen J, Wang BR, Zhu YW, Xu Y, Wang J, Xiao H, Shi JP, Zhang YD, Xu J (2011) Short amyloid-beta immunogens show strong immunogenicity and avoid stimulating pro-inflammatory pathways in bone marrow-derived dendritic cells from C57BL/6 J mice in vitro. Peptides 32(8):1617–1625. doi:10.1016/j.peptides.2011.06.013

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Nussenzweig MC (2002) Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 99(1):351–358. doi:10.1073/pnas.231606698

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Ann Rev Immunol 21:685–711. doi:10.1146/annurev.immunol.21.120601.141040

    Article  CAS  Google Scholar 

  • te Velde AA, van Kooyk Y, Braat H, Hommes DW, Dellemijn TA, Slors JF, van Deventer SJ, Vyth-Dreese FA (2003) Increased expression of DC-SIGN+IL-12+IL-18+ and CD83+IL-12-IL-18- dendritic cell populations in the colonic mucosa of patients with Crohn’s disease. Eur J Immunol 33(1):143–151. doi:10.1002/immu.200390017

    Article  Google Scholar 

  • Trevejo JM, Marino MW, Philpott N, Josien R, Richards EC, Elkon KB, Falck-Pedersen E (2001) TNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection. Proc Natl Acad Sci USA 98(21):12162–12167. doi:10.1073/pnas.211423598

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wesa AK, Galy A (2001) IL-1 beta induces dendritic cells to produce IL-12. Int Immunol 13(8):1053–1061

    Article  CAS  PubMed  Google Scholar 

  • Yoon MS, Lee JS, Choi BM, Jeong YI, Lee CM, Park JH, Moon Y, Sung SC, Lee SK, Chang YH, Chung HY, Park YM (2006) Apigenin inhibits immunostimulatory function of dendritic cells: Implication of immunotherapeutic adjuvant. Mol Pharmacol 70(3):1033–1044. doi:10.1124/mol.106.024547

    Article  CAS  PubMed  Google Scholar 

  • Zeng X, Wang T, Zhu C, Xing X, Ye Y, Lai X, Song B, Zeng Y (2012) Topographical and biological evidence revealed FTY720-mediated anergy-polarization of mouse bone marrow-derived dendritic cells in vitro. PLoS One 7(5):e34830. doi:10.1371/journal.pone.0034830

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zou S, Shen X, Tang Y, Fu Z, Zheng Q, Wang Q (2010) Astilbin suppresses acute heart allograft rejection by inhibiting maturation and function of dendritic cells in mice. Transplant Proc 42(9):3798–3802. doi:10.1016/j.transproceed.2010.06.031

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (31172302 and 31372465) and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflict of interest

The authors have no financial conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qian Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yin, Y., Qin, T., Yu, Q. et al. Bursopentin (BP5) from chicken bursa of fabricius attenuates the immune function of dendritic cells. Amino Acids 46, 1763–1774 (2014). https://doi.org/10.1007/s00726-014-1735-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-014-1735-x

Keywords

Navigation