Information de reference pour ce titreAccession Number: | 00078328-200908000-00006.
|
Author: | Neves, Bruno Miguel a,b; Cruz, Maria Teresa a,b,*; Francisco, Vera b,e; Garcia-Rodriguez, Carmen c; Silvestre, Ricardo d; Cordeiro-da-Silva, Anabela d; Dinis, Augusto M. e; Batista, Maria Teresa a,e; Duarte, Carlos B. b; Lopes, Maria Celeste a,b
|
Institution: | (a) Faculdade de Farmacia, Universidade de Coimbra, Coimbra, Portugal (b) Centro de Neurociencias e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal (c) Instituto de Biologia y Genetica Molecular, Universidad de Valladolid - CSIC, Valladolid, Spain (d) Faculdade de Farmacia e Instituto de Biologia Molecular e Celular da Universidade do Porto, Porto, Portugal (e) Centro de Estudos Farmaceuticos, Universidade de Coimbra, Coimbra, Portugal
|
Title: | Differential roles of PI3-Kinase, MAPKs and NF-[kappa]B on the manipulation of dendritic cell Th1/Th2 cytokine/chemokine polarizing profile.[Article]
|
Source: | Molecular Immunology. 46(13):2481-2492, August 2009.
|
Abstract: | : Dendritic cells (DC) are professional antigen-presenting cells with a unique capacity to initiate and modulate immune responses by their ability to prime naive T-cells. Upon stimuli, DC experience several morphologic, phenotypic and functional changes in a process referred to as maturation. This process is crucial to the biological functions of DC since their maturation status confer them the ability to polarize distinct T-cell subsets. In this work we explored the relevance of PI3-Kinase, Mitogen-Activated Protein Kinases (MAPKs) and NF-kappaB on cytokines/chemokines and co-stimulatory molecules expression. As experimental model, we used a fetal skin-derived dendritic cell line (FSDC) induced to mature by treatment with lipopolysaccharide (LPS). Morphology and ultrastructure were analyzed by confocal and electron microscopies, respectively. Levels of phosphorylated proteins were evaluated by Western blot, production of cytokines/chemokines was analyzed by protein arrays and the expression of surface molecules was evaluated by flow cytometry. The effect of specific inhibitors of the studied signaling pathways on the transcription of cytokines/chemokines and co-stimulatory molecules was accessed by Quantitative Real-Time RT-PCR. The results showed that LPS induces significant morphological and ultrastructural changes in FSDC. Western blot analysis revealed that LPS challenge promotes an early and transient activation of NF-[kappa]B, ERK1/2, p38 MAPK, along with a more sustained PI3 kinase/AKT activation. The co-stimulatory CD40, CD80, CD86 and antigen-presenting MHC class I and II molecules were increased and among secreted molecules, interleukin IL-6, CCL5, G-CSF, CCL2, CXCL2 were strongly up-regulated. Using a pharmacological approach we observed that LPS-induced increase of these molecules was differentially regulated by the distinct signaling pathways. Moreover, the polarizing Th2 cytokines/chemokines induced by LPS in FSDC were found to be positively regulated by NF-[kappa]B and ERK and negatively modulated by p38 MAPK. Altogether these results suggest that the use of pharmacological inhibitors to manipulate DC maturation, namely the polarizing Th1/Th2 cytokine/chemokine profile, may be useful in the development of more specific immunotherapeutic protocols.
(C) 2009Elsevier, Inc.
|
Author Keywords: | Dendritic cells; T-cell polarization; Signal transduction pathways; Cytokines; Chemokines.
|
References: | Aiba S., 1998. Maturation of dendritic cells induced by cytokines and haptens. Tohoku J. Exp. Med. 184, 159-172.
Aiba S., Tagami H., 1998. Dendritic cell activation induced by various stimuli, e.g. exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellular matrix. J. Dermatol. Sci. 20, 1-13.
Ajuebor M.N., Hogaboam C.M., Kunkel S.L., Proudfoot A.E., Wallace J.L., 2001. The chemokine RANTES is a crucial mediator of the progression from acute to chronic colitis in the rat. J. Immunol. 166, 552-558.
An H., Yu Y., Zhang M., Xu H., Qi R., Yan X., Liu S., Wang W., Guo Z., Guo J., Qin Z., Cao X., 2002. Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology. 106, 38-45.
Arrighi J.F., Rebsamen M., Rousset F., Kindler V., Hauser C., 2001. A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers. J. Immunol. 166, 3837-3845.
Azenshtein E., Luboshits G., Shina S., Neumark E., Shahbazian D., Weil M., Wigler N., Keydar I., Ben-Baruch A., 2002. The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. Cancer Res. 62, 1093-1102.
Banchereau J., Briere F., Caux C., Davoust J., Lebecque S., Liu Y.J., Pulendran B., Palucka K., 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767-811.
Banchereau J., Palucka A.K., 2005. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol. 5, 296-306.
Banchereau J., Steinman R.M., 1998. Dendritic cells and the control of immunity. Nature. 392, 245-252.
Barnes D.A., Tse J., Kaufhold M., Owen M., Hesselgesser J., Strieter R., Horuk R., Perez H.D., 1998. Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J. Clin. Invest. 101, 2910-2919.
Blanco P., Palucka A.K., Pascual V., Banchereau J., 2008. Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 19, 41-52.
Bober L.A., Grace M.J., Pugliese-Sivo C., Rojas-Triana A., Sullivan L.M., Narula S.K., 1995. The effects of colony stimulating factors on human monocyte cell function. Int. J. Immunopharmacol. 17, 385-392.
Cella M., Salio M., Sakakibara Y., Langen H., Julkunen I., Lanzavecchia A., 1999. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J. Exp. Med. 189, 821-829.
Cella M., Scheidegger D., Palmer-Lehmann K., Lane P., Lanzavecchia A., Alber G., 1996. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184, 747-752.
Cruz M.T., Duarte C.B., Goncalo M., Carvalho A.P., Lopes M.C., 2001. LPS induction of I kappa B-alpha degradation and iNOS expression in a skin dendritic cell line is prevented by the janus kinase 2 inhibitor, Tyrphostin b42. Nitric Oxide. 5, 53-61.
De Smedt T., Pajak B., Muraille E., Lespagnard L., Heinen E., De Baetselier P., Urbain J., Leo O., Moser M., 1996. Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J. Exp. Med. 184, 1413-1424.
Diehl S., Rincon M., 2002. The two faces of IL-6 on Th1/Th2 differentiation. Mol. Immunol. 39, 531-536.
Dinis, A.M., Cruz, M.T., Lopes, M.C., Batista, M.T., 2009. A light, scanning electron and transmission electron microscopic study of a fetal mouse skin dendritic cell line (FSDC). Microsc. Microanal. in press.
Dowling D., Hamilton C.M., O'Neill S.M., 2008. A comparative analysis of cytokine responses, cell surface marker expression and MAPKs in DCs matured with LPS compared with a panel of TLR ligands. Cytokine. 41, 254-262.
Girolomoni G., Lutz M.B., Pastore S., Assmann C.U., Cavani A., Ricciardi-Castagnoli P., 1995. Establishment of a cell line with features of early dendritic cell precursors from fetal mouse skin. Eur. J. Immunol. 25, 2163-2169.
Goede V., Brogelli L., Ziche M., Augustin H.G., 1999. Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int. J. Cancer. 82, 765-770.
Gu L., Tseng S., Horner R.M., Tam C., Loda M., Rollins B.J., 2000. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature. 404, 407-411.
Guha M., Mackman N., 2002. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J. Biol. Chem. 277, 32124-32132.
Hacker H., Mischak H., Miethke T., Liptay S., Schmid R., Sparwasser T., Heeg K., Lipford G.B., Wagner H., 1998. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J. 17, 6230-6240.
Hartmann G., Weiner G.J., Krieg A.M., 1999. CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 96, 9305-9310.
Hazeki K., Kinoshita S., Matsumura T., Nigorikawa K., Kubo H., Hazeki O., 2006. Opposite effects of wortmannin and 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride on toll-like receptor-mediated nitric oxide production: negative regulation of nuclear factor-{kappa}B by phosphoinositide 3-kinase. Mol. Pharmacol. 69, 1717-1724.
Horng T., Barton G.M., Medzhitov R., 2001. TIRAP: an adapter molecule in the Toll signaling pathway. Nat. Immunol. 2, 835-841.
Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S., 1999. 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.
Huang A.Y., Golumbek P., Ahmadzadeh M., Jaffee E., Pardoll D., Levitsky H., 1994. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science. 264, 961-965.
Ichim T.E., Zhong R., Min W.P., 2003. Prevention of allograft rejection by in vitro generated tolerogenic dendritic cells. Transpl. Immunol. 11, 295-306.
Jonuleit H., Kuhn U., Muller G., Steinbrink K., Paragnik L., Schmitt E., Knop J., Enk A.H., 1997. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol. 27, 3135-3142.
Kaisho T., Takeuchi O., Kawai T., Hoshino K., Akira S., 2001. Endotoxin-induced maturation of MyD88-deficient dendritic cells. J. Immunol. 166, 5688-5694.
Kared H., Masson A., Adle-Biassette H., Bach J.F., Chatenoud L., Zavala F., 2005. Treatment with granulocyte colony-stimulating factor prevents diabetes in NOD mice by recruiting plasmacytoid dendritic cells and functional CD4(+)CD25(+) regulatory T-cells. Diabetes. 54, 78-84.
Karpus W.J., Lukacs N.W., Kennedy K.J., Smith W.S., Hurst S.D., Barrett T.A., 1997. Differential CC chemokine-induced enhancement of T helper cell cytokine production. J. Immunol. 158, 4129-4136.
Kawai T., Takeuchi O., Fujita T., Inoue J., Muhlradt P.F., Sato S., Hoshino K., Akira S., 2001. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167, 5887-5894.
Kim Y.H., Choi K.H., Park J.W., Kwon T.K., 2005. LY294002 inhibits LPS-induced NO production through a inhibition of NF-kappaB activation: independent mechanism of phosphatidylinositol 3-kinase. Immunol. Lett. 99, 45-50.
Korn T., Mitsdoerffer M., Croxford A.L., Awasthi A., Dardalhon V.A., Galileos G., Vollmar P., Stritesky G.L., Kaplan M.H., Waisman A., Kuchroo V.K., Oukka M., 2008. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. U.S.A. 105, 18460-18465.
Lieschke G.J., Grail D., Hodgson G., Metcalf D., Stanley E., Cheers C., Fowler K.J., Basu S., Zhan Y.F., Dunn A.R., 1994. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood. 84, 1737-1746.
Lu B., Rutledge B.J., Gu L., Fiorillo J., Lukacs N.W., Kunkel S.L., North R., Gerard C., Rollins B.J., 1998. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J. Exp. Med. 187, 601-608.
Luther S.A., Cyster J.G., 2001. Chemokines as regulators of T cell differentiation. Nat. Immunol. 2, 102-107.
Makino Y., Cook D.N., Smithies O., Hwang O.Y., Neilson E.G., Turka L.A., Sato H., Wells A.D., Danoff T.M., 2002. Impaired T cell function in RANTES-deficient mice. Clin. Immunol. 102, 302-309.
McColl S.R., 2002. Chemokines and dendritic cells: a crucial alliance. Immunol. Cell Biol. 80, 489-496.
Mellman I., Steinman R.M., 2001. Dendritic cells: specialized and regulated antigen processing machines. Cell. 106, 255-258.
Miller S.I., Ernst R.K., Bader M.W., 2005. LPS, TLR4 and infectious disease diversity. Nat. Rev. Microbiol. 3, 36-46.
Moore K.W., de Waal Malefyt R., Coffman R.L., O'Garra A., 2001. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683-765.
Mrowietz U., Schwenk U., Maune S., Bartels J., Kupper M., Fichtner I., Schroder J.M., Schadendorf D., 1999. The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice. Br. J. Cancer. 79, 1025-1031.
Musial A., Eissa N.T., 2001. Inducible nitric-oxide synthase is regulated by the proteasome degradation pathway. J. Biol. Chem. 276, 24268-24273.
Muthuswamy R., Urban J., Lee J.J., Reinhart T.A., Bartlett D., Kalinski P., 2008. Ability of mature dendritic cells to interact with regulatory T cells is imprinted during maturation. Cancer Res. 68, 5972-5978.
Nachbaur D., Kircher B., 2005. Dendritic cells in allogeneic hematopoietic stem cell transplantation. Leuk. Lymphoma. 46, 1387-1396.
Nakahara T., Moroi Y., Uchi H., Furue M., 2006. Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement. J. Dermatol. Sci. 42, 1-11.
Nakahara T., Uchi H., Urabe K., Chen Q., Furue M., Moroi Y., 2004. Role of c-Jun N-terminal kinase on lipopolysaccharide induced maturation of human monocyte-derived dendritic cells. Int. Immunol. 16, 1701-1709.
Neves B.M., Cruz M.T., Francisco V., Goncalo M., Figueiredo A., Duarte C.B., Lopes M.C., 2008. Differential modulation of CXCR4 and CD40 protein levels by skin sensitizers and irritants in the FSDC cell line. Toxicol. Lett. 177, 74-82.
Nouri-Shirazi M., Banchereau J., Fay J., Palucka K., 2000. Dendritic cell based tumor vaccines. Immunol. Lett. 74, 5-10.
Pan L., Delmonte Jr J. Jr, Jalonen C.K., Ferrara J.L., 1995. Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood. 86, 4422-4429.
Patel T.R., Corbett S.A., 2004. Simvastatin suppresses LPS-induced Akt phosphorylation in the human monocyte cell line THP-1. J. Surg. Res. 116, 116-120.
Pfaffl M.W., 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45.
Poltorak A., He X., Smirnova I., Liu M.Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M., Galanos C., Freudenberg M., Ricciardi-Castagnoli P., Layton B., Beutler B., 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 282, 2085-2088.
Rescigno M., Granucci F., Citterio S., Foti M., Ricciardi-Castagnoli P., 1999. Coordinated events during bacteria-induced DC maturation. Immunol. Today. 20, 200-203.
Rescigno M., Martino M., Sutherland C.L., Gold M.R., Ricciardi-Castagnoli P., 1998. Dendritic cell survival and maturation are regulated by different signaling pathways. J. Exp. Med. 188, 2175-2180.
Roake J.A., Rao A.S., Morris P.J., Larsen C.P., Hankins D.F., Austyn J.M., 1995. Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. J. Exp. Med. 181, 2237-2247.
Sallusto F., Schaerli P., Loetscher P., Schaniel C., Lenig D., Mackay C.R., Qin S., Lanzavecchia A., 1998. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur. J. Immunol. 28, 2760-2769.
Sato K., Yamashita N., Baba M., Matsuyama T., 2003. Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells. Blood. 101, 3581-3589.
Schrum S., Probst P., Fleischer B., Zipfel P.F., 1996. Synthesis of the CC-chemokines MIP-1alpha, MIP-1beta, and RANTES is associated with a type 1 immune response. J. Immunol. 157, 3598-3604.
Shen H., Tesar B.M., Walker W.E., Goldstein D.R., 2008. Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation. J. Immunol. 181, 1849-1858.
Shen Z., Reznikoff G., Dranoff G., Rock K.L., 1997. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J. Immunol. 158, 2723-2730.
Sigal L.J., Crotty S., Andino R., Rock K.L., 1999. Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature. 398, 77-80.
Siveke J.T., Hamann A., 1998. T helper 1 and T helper 2 cells respond differentially to chemokines. J. Immunol. 160, 550-554.
Sloand E.M., Kim S., Maciejewski J.P., Van Rhee F., Chaudhuri A., Barrett J., Young N.S., 2000. Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo. Blood. 95, 2269-2274.
Steinman R.M., Banchereau J., 2007. Taking dendritic cells into medicine. Nature. 449, 419-426.
Verhasselt V., Buelens C., Willems F., De Groote D., Haeffner-Cavaillon N., Goldman M., 1997. Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. J. Immunol. 158, 2919-2925.
Vicari A.P., Caux C., 2002. Chemokines in cancer. Cytokine Growth Factor Rev. 13, 143-154.
Viola A., Molon B., Contento R.L., 2008. Chemokines: coded messages for T-cell missions. Front. Biosci. 13, 6341-6353.
Waldner H., 2009. The role of innate immune responses in autoimmune disease development. Autoimmun. Rev. 8, 400-404.
Winzler C., Rovere P., Rescigno M., Granucci F., Penna G., Adorini L., Zimmermann V.S., Davoust J., Ricciardi-Castagnoli P., 1997. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J. Exp. Med. 185, 317-328.
Xu L., Duan L., Cao K., Yuan G., Peng Y., Huang X., Xiang P., Li S., 2007. Predominant immature CD8alpha+ dendritic cells prevent graft-vs.-host disease but do not increase the risk of leukemia recurrence. Eur. J. Haematol. 78, 235-245.
|
Language: | English.
|
Document Type: | Articles.
|
Journal Subset: | Life & Biomedical Sciences.
|
ISSN: | 0161-5890
|
DOI Number: | https://dx.doi.org/10.1016/j.mol...- ouverture dans une nouvelle fenêtre
|
Annotation(s) | |
|
|