Rhamnogalacturonan II is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8þ T cells

다국어 초록 (Multilingual Abstract)

We evaluated the effectiveness of rhamnogalacturonan II (RG-II)-stimulated bone marrow-derived dendritic cells (BMDCs)vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin (OVA). BMDCs treated with RG-II had an activated phenotype. RG-II induced interleukin (IL)-12, IL-1b, tumor necrosis factor-a (TNF-a) and interferon-c (IFN-c) production during dendritic cell (DC) maturation. BMDCs stimulated with RG-II facilitate the proliferation of CD8þ T cells. Using BMDCs from the mice deficient in Toll-like receptors (TLRs), we revealed that RG-II activity is dependent on TLR4. RG-II showed a preventive effect of immunization with OVA-pulsed BMDCs against EG7 lymphoma. These results suggested that RG-II expedites the DC-based immune response through the TLR4signaling pathway.

참고문헌 (Reference)

1 Mauri C, "Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmune inflammatory process" 6 : 673-679, 2000

2 Schuler G, "The use of dendritic cells in cancer immunotherapy" 15 : 138-147, 2003

3 Dodeller F, "The p38 mitogen-activated protein kinase regulates effector functions of primary human CD4 T cells" 35 : 3631-3642, 2005

4 Clarke SR, "The critical role of CD40/CD40L in the CD4-dependent generation of CD8þ T cell immunity" 67 : 607-614, 2000

5 노경태, "The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency" 생화학분자생물학회 44 (44): 340-349, 2012

6 Sharpe AH, "The B7-CD28 superfamily" 2 : 116-126, 2002

7 Trevejo JM, "TNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection" 98 : 12162-12167, 2001

8 Jiang Y, "TLR4 signaling induces functional nerve growth factor receptor p75NTR on mouse dendritic cells via p38MAPK and NF-kappa B pathways" 45 : 1557-1566, 2008

9 Schoenberger SP, "T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions" 393 : 480-483, 1998

10 Darvill AG, "Structure of plant cell walls: VIII. A new pectic polysaccharide" 62 : 418-422, 1978

11 Napolitani G, "Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells" 6 : 769-776, 2005

12 O’Neill MA, "Rhamnogalacturonan II: structure and function of a borate cross-linked cell wall pectic polysaccharide" 55 : 109-139, 2004

13 Shin KS, "Rhamnogalacturonan II from the leaves of Panax ginseng C.A. Meyer as a macrophage Fc receptor expression-enhancing polysaccharide" 300 : 239-249, 1997

14 Subramanian L, "Resveratrol: challenges in translation to the clinic–a critical discussion" 16 : 5942-5948, 2010

15 Li T, "Resveratrol induces apoptosis, influences IL-6 and exerts immunomodulatory effect on mouse lymphocytic leukemia both in vitro and in vivo" 7 : 1221-1231, 2007

16 정인덕, "RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction" 생화학분자생물학회 45 (45): 79-84, 2012

17 Noh KT, "Protein kinase C delta(PKCdelta)-extracellular signal-regulated kinase 1/2(ERK1/ 2)signaling cascade regulates glycogen synthase kinase-3(GSK-3)inhibition-mediated interleukin-10(IL-10)expression in lipopolysaccharide(LPS)-induced endotoxemia" 287 : 14226-14233, 2012

18 Fields RC, "Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo" 95 : 9482-9487, 1998

19 Adams S, "Maturation matters: importance of maturation for antitumor immunity of dendritic cell vaccines" 22 : 3834-3835, 2004

20 Akira S, "Mammalian Toll-like receptors" 15 : 5-11, 2003

21 Yano S, "Macrophage colony-stimulating factor gene transduction into human lung cancer cells differentially regulates metastasis formations in various organ microenvironments of natural killer cell-depleted SCID mice" 57 : 784-790, 1997

22 Broomfield SA, "Locally administered TLR7 agonists drive systemic antitumor immune responses that are enhanced by anti-CD40 immunotherapy" 182 : 5217-5224, 2009

23 Heufler C, "Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells" 26 : 659-668, 1996

24 Rodeberg DA, "In vitro induction of immune responses to shared tumor-associated antigens in rhabdomyosarcoma" 42 : 1396-1402, 2007

25 Portielje JE, "IL-12: a promising adjuvant for cancer vaccination" 52 : 133-144, 2003

26 Attele AS, "Ginseng pharmacology: multiple constituents and multiple actions" 58 : 1685-1693, 1999

27 Chan T, "Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat shock protein 70 gene-transfected tumor cells in early phase of apoptosis" 14 : 409-420, 2007

28 Chi H, "Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses" 103 : 2274-2279, 2006

29 Nakahara T, "Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement" 42 : 1-11, 2006

30 Gilboa E, "DC-based cancer vaccines" 117 : 1195-1203, 2007

31 Jeong YI, "Curcumin suppresses the induction of indoleamine 2,3-dioxygenase by blocking the Janus-activated kinase-protein kinase Cdelta-STAT1 signaling pathway in interferon-gamma-stimulated murine dendritic cells" 284 : 3700-3708, 2009

32 Brode S, "Cross-presentation: dendritic cells and macrophages bite off more than they can chew!" 112 : 345-351, 2004

33 Sanchez PJ, "Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo" 178 : 1564-1572, 2007

34 Gao QP, "Chemical properties and anticomplementary activities of polysaccharide fractions from roots and leaves of Panax ginseng" 55 : 9-12, 1989

35 Terheyden P, "CD40-ligated dendritic cells effectively expand melanoma-specific CD8þ CTLs and CD4þ IFN-gamma-producing T cells from tumor-infiltrating lymphocytes" 164 : 6633-6639, 2000

36 Moodycliffe AM, "CD40-CD40 ligand interactions in vivo regulate migration of antigen-bearing dendritic cells from the skin to draining lymph nodes" 191 : 2011-2020, 2000

37 French RR, "CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help" 5 : 548-553, 1999

38 Yanagawa Y, "CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities" 101 : 4923-4929, 2003

39 Marsland BJ, "CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells" 22 : 493-505, 2005

40 Tatsumi T, "Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma" 61 : 7563-7567, 2001

41 Audibert F, "Adjuvants for vaccines, a quest" 3 : 1187-1193, 2003

42 Steinman RM, "Active immunization against cancer with dendritic cells: the near future" 94 : 459-473, 2001

43 Geissmann F, "Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin" 196 : 417-430, 2002

44 Datta SK, "A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells" 170 : 4102-4110, 2003