Lycium barbarum polysaccharides induce Toll‑like receptor 2‑ and 4‑mediated phenotypic and functional maturation of murine dendritic cells via activation of NF‑κB

Zhu,Jie; Zhang,Yuanyuan; Shen,Yueshuang; Zhou,Huanqin; Yu,Xiaomei

doi:10.3892/mmr.2013.1608

Lycium barbarum polysaccharides induce Toll‑like receptor 2‑ and 4‑mediated phenotypic and functional maturation of murine dendritic cells via activation of NF‑κB

Authors:
- Jie Zhu
- Yuanyuan Zhang
- Yueshuang Shen
- Huanqin Zhou
- Xiaomei Yu
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Affiliations: Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China, Department of Respiratory Medicine, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
Published online on: July 31, 2013 https://doi.org/10.3892/mmr.2013.1608
Pages: 1216-1220

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Abstract

Dendritic cells (DCs) are potent antigen‑presenting cells that play pivotal roles in the initiation of primary immune responses. Lycium barbarum polysaccharides (LBPs) are known to have a variety of immunomodulatory functions. However, the cellular and molecular mechanisms underlying their therapeutic effects are poorly understood. In this study, we report that LBPs induce phenotypic and functional maturation of DCs. LBPs upregulated DC expression of I‑A/I‑E and CD11c, enhanced DC allostimulatory activity and induced IL‑12p40 production. Furthermore, the activity of LBPs on DCs was significantly reduced by treating the cells with anti‑TLR2 or anti‑TLR4 antibody prior to LBPs, indicating that both are possible receptors of LBPs. Maturation of DCs by LBPs was able to directly activate the nuclear transcription factor NF‑κB p65. The results revealed that LBP stimulation induces the phenotypic and functional maturation of DCs via TLR2- and/or TLR4-mediated NF‑κB signaling pathways.

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1	Banchereau J, Briere F, Caux C, et al: Immunobiology of dendritic cells. Annu Rev Immunol. 18:767–811. 2000. View Article : Google Scholar
2	Banchereau J and Steinman RM: Dendritic cells and the control of immunity. Nature. 392:245–252. 1998. View Article : Google Scholar
3	Lanzavecchia A and Sallusto F: Regulation of T cell immunity by dendritic cells. Cell. 106:263–266. 2001. View Article : Google Scholar : PubMed/NCBI
4	Liu YJ: Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell. 106:259–262. 2001. View Article : Google Scholar : PubMed/NCBI
5	Austyn JM, Kupiec-Weglinski JW, Hankins DF and Morris PJ: Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and bingding within marginal zone. J Exp Med. 167:646–651. 1988. View Article : Google Scholar : PubMed/NCBI
6	Rock KL: A new foreign policy: MHC class I molecules monitor the outside world. Immunol Today. 17:131–137. 1996. View Article : Google Scholar : PubMed/NCBI
7	De Smedt T, Pajak B, Muraille E, et al: Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J Exp Med. 184:1413–1424. 1996.PubMed/NCBI
8	Cella M, Sallusto F and Lanzavecchia A: Origin, maturation and antigen presenting function of dendritic cells. Curr poin Immunol. 9:10–16. 1997. View Article : Google Scholar
9	Salio M, Cerundolo V and Lanzavecchia A: Dendritic cell maturation is induced by mycoplasma infection but not by necrotic cells. Eur J Immunol. 30:705–708. 2000. View Article : Google Scholar : PubMed/NCBI
10	Kolb-Maurer A, Gentschev I, Fries HW, et al: Listeria monocytogenes-infected human dendritic cells: uptake and host cell response. Infect Immun. 68:3680–3686. 2000. View Article : Google Scholar
11	Marovich MA, McDowell MA, Thomas EK and Nutman TB: IL-12p70 production by Leishmania major-harboring human dendritic cells is a CD40/CD40 ligand-dependent process. J Immunol. 164:5858–5865. 2000. View Article : Google Scholar : PubMed/NCBI
12	Shao P, Zhao LH, Zhi-Chen, et al: Regulation on maturation and function of dendritic cells by Astragalus mongholicus polysaccharides. Int Immunopharmacol. 6:1161–1166. 2006. View Article : Google Scholar : PubMed/NCBI
13	Aliprantis AO, Yang RB, Mark MR, et al: Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science. 285:736–739. 1999. View Article : Google Scholar : PubMed/NCBI
14	Brightbill HD, Libraty DH, Krutzik SR, et al: Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 285:732–736. 1999. View Article : Google Scholar : PubMed/NCBI
15	Hirschfeld M, Kirschning CJ, Schwandner R, et al: Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J Immunol. 163:2382–2386. 1999.PubMed/NCBI
16	Takeuchi O, Kaufmann A, Grote K, et al: Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pathway. J Immunol. 164:554–557. 2000. View Article : Google Scholar
17	Hoshino K, Takeuchi O, Kawai T, et al: Cutting edge: toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 162:3749–3752. 1999.PubMed/NCBI
18	Arbour NC, Lorenz E, Schutte BC, et al: TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 25:187–191. 2000. View Article : Google Scholar : PubMed/NCBI
19	Krieg AM and Waqner H: Causing a commotion in the blood: immunotherapy progresses from bacteria to bacterial DNA. Immunol Today. 21:521–526. 2000. View Article : Google Scholar : PubMed/NCBI
20	May MJ and Ghosh S: Signal transduction through NF-κB. Immunol Today. 19:80–88. 1998.
21	Yang RB, Mark MR, Gurney AL and Godowski PJ: Signaling events induced by lipopolysaccharide-activated toll-like receptor 2. Immunol. 163:639–643. 1999.PubMed/NCBI
22	Zhu J, Zhao LH, Zhao XP, et al: Lycium barbarum polysaccharides regulate phenotypic and functional maturation of murine dendritic cells. Cell Biol Int. 31:615–619. 2007. View Article : Google Scholar
23	Inaba K, Inaba M, Romani N, Aya H, et al: Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 176:1693–1702. 1992. View Article : Google Scholar : PubMed/NCBI
24	Sallusto F and Lanzavecchia A: Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimalating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J Exp Med. 179:1109–1118. 1994.PubMed/NCBI
25	Winzler C, Rovere P, Resciqno M, et al: Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J Exp Med. 185:317–328. 1997. View Article : Google Scholar : PubMed/NCBI
26	Roake JA, Rao AS, Morris PJ, et al: Dendritic cells loss from nonlymphoid tissues after systemic administration of lipopolysaccharides, tumor necrosis factor, and interleukin 1. J Exp Med. 181:2237–2247. 1995. View Article : Google Scholar : PubMed/NCBI
27	Cao LZ and Lin ZB: Regulation on maturation and function of dendritic cells by Ganoderma lucidum polysaccharides. Immunol Lett. 83:163–169. 2002. View Article : Google Scholar : PubMed/NCBI
28	Park SK, Kim GY, Lim JY, et al: Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells. Biochem Biophys Res Commun. 312:449–458. 2003. View Article : Google Scholar : PubMed/NCBI
29	Kanazawa M, Mori Y, Yoshihara K, et al: Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes. Immunol Lett. 91:229–238. 2004. View Article : Google Scholar : PubMed/NCBI
30	Means TK, Pavlovich RP, Roca D, et al: Activation of TNF-α transcription utilizes distinct MAP kinase pathways in different macrophage populations. J Leukoc Biol. 67:885–893. 2000.
31	Martin M, Michalek SM and Katz J: Role of innate immune factors in the adjuvant activity of monophosphoryl lipid A. Infec Immun. 71:2498–2507. 2003. View Article : Google Scholar : PubMed/NCBI
32	Tapping RI, Akashi S, Miyake K, et al: Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. Immunol. 165:5780–5787. 2000. View Article : Google Scholar : PubMed/NCBI