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Contact sensitizers downregulate the expression of the chemokine receptors CCR6 and CXCR4 in a skin dendritic cell line

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Abstract

Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response, namely in allergic contact dermatitis (ACD). In this work, we investigated by flow cytometry the effect of the contact sensitizers 2,4-dinitrofluorobenzene (DNFB), 1,4-phenylenediamine (PPD) and nickel sulfate (NiSO4), on the surface expression of the chemokine receptors CCR6 and CXCR4 in DC. As an experimental model of a DC we used a fetal skin-derived dendritic cell line (FSDC), which has morphological, phenotypical and functional characteristics of skin DC. Our results show that all the skin sensitizers studied decreased the membrane expression of the chemokine receptors CCR6 and CXCR4. In contrast, 2,4-dichloronitrobenzene (DCNB), the inactive analogue of DNFB without contact sensitizing properties, was without effect on the surface expression of these receptors. Lipopolysaccharide (LPS), which induces the maturation of DC, also reduced surface CCR6 and CXCR4 expression.

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Abbreviations

ACD:

Allergic contact dermatitis

DC:

Dendritic cell

DCNB:

2,4-Dichloronitrobenzene

DMSO:

Dimethyl sulphoxide

DNFB:

2,4-Dinitrofluorobenzene

FSDC:

Fetal skin dendritic cell line

LC:

Langerhans cells

LPS:

Lipopolysaccharide

MFI:

Mean fluorescence intensity

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

PPD:

1,4-Phenylenediamine

References

  1. Cumberbatch M, Dearman RJ, Griffiths CE, Kimber I (2000) Langerhans cell migration. Clin Exp Dermatol 25:413–418

    Article  PubMed  CAS  Google Scholar 

  2. Sozzani S, Allavena P, Vecchi A, Mantovani A (2000) Chemokines and dendritic cell traffic. J Clin Immunol 20:151–159

    Article  PubMed  CAS  Google Scholar 

  3. Proudfoot AEI (2002) Chemokine receptors: multifaceted therapeutic targets. Nat Rev Immunol 2:106–115

    Article  PubMed  CAS  Google Scholar 

  4. Onuffer JJ, Horuk R (2002) Chemokines, chemokines receptors and small-molecules antagonists: recent developments. Trends Pharmacol Sci 23:459–467

    Article  PubMed  CAS  Google Scholar 

  5. Girolomoni G, Lutz MB, Pastore S, Abmann CU, 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

    Article  PubMed  CAS  Google Scholar 

  6. Cruz MT, Duarte CB, Gonçalo M, Carvalho AP, Lopes MC (1999) Involvement of JAK2 and MAPK on type II nitric oxide synthase expression in skin-derived dendritic cells. Am J Physiol 277:C1050–C1057

    PubMed  CAS  Google Scholar 

  7. Cruz MT, Duarte CB, Gonçalo M, Carvalho AP, Lopes MC (2001) LPS induction of IkB-αdegradation and iNOS expression in a skin dendritic cell line is prevented by the Janus kinase 2 inhibitor, tyrphostin B42. Nitric Oxide Biol Chem 5:53–61

    Article  CAS  Google Scholar 

  8. Rescigno M, Granucci F, Ricciardi-Castagnoli P (2000) Molecular events of bacterial-induced maturation of dendritic cells. J Clin Immunol 20:161–166

    Article  PubMed  CAS  Google Scholar 

  9. Becker D, Neiß U, Neis S, Reske K, Knop J (1992) Contact allergens modulate the expression of MHC class II molecules on murine epidermal Langerhans cells by endocytic mechanisms. J Invest Dermatol 98:700–705

    Article  PubMed  CAS  Google Scholar 

  10. Kuhn U, Brand P, Willemsen J, Jonuleit H, Enk AH, van Brandwijk-Petershans R, Saloga J, Knop J, Becker D (1998) Induction of tyrosine phosphorylation in human MHC class II-positive antigen-presenting cells by stimulation with contact sensitizers. J Immunol 160:667–673

    PubMed  CAS  Google Scholar 

  11. Manome H, Aiba S, Tagami H (1999) Simple chemicals can induce maturation and apoptosis of dendritic cells. Immunol 98:481–490

    Article  CAS  Google Scholar 

  12. Wang B, Esche C, Mamelak A, Freed I, Watanabe H, Sauder DN (2003) Cytokine knockouts in contact hypersensitivity research. Cytokine Growth factor Rev 14:381–389

    Article  PubMed  CAS  Google Scholar 

  13. Vital AL, Gonçalo M, Cruz MT, Duarte CB, Figueiredo A, Carvalho AP, Lopes MC (2005) The sensitizers nickel sulfate and 2,4-dinitrofluorobenzene induce the expression of CD40 and IL-12 receptor in a fetal skin dendritic cell line. Biosci Rep (in press)

  14. Carramolino L, Kremer L, Goya I, Varona R, Buesa JM, Gutierrez J, Zaballos A, Martinez-A C, Marquez G (1999) Down-regulation of the beta-chemokine receptor CCR6 in dendritic cells mediated by TNF-alpha and IL-4. J Leukoc Biol 66:837–844

    PubMed  CAS  Google Scholar 

  15. Kaisho T, Takeuchi O, Kawai T, Hoshino K, Akira S (2001) Endotoxin-induced maturation of MyD88-deficient dendritic cells. J Immunol 166:5688–5694

    PubMed  CAS  Google Scholar 

  16. Ismaili J, Rennesson J, Aksoy E, Vekemans J, Vincart B, Amraoui Z, Van Laethem F, Goldman M, Dubois PM (2002) Monophosphoryl lipid A activates both human dendritic cells and T cells. J Immunol 168: 926–932

    PubMed  CAS  Google Scholar 

  17. Tuschl H, Kovac R (2001) Langerhans cells and immature dendritic cells as model systems for screening of skin sensitizers. Toxicol In Vitro 15:327–331

    Article  PubMed  CAS  Google Scholar 

  18. Arrighi JF, 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

    PubMed  CAS  Google Scholar 

  19. Becker D, Valk E, Zahn S, Brand P, Knop J (2003) Coupling of contact sensitizers to thiol groups is a key event for the activation of monocytes and monocyte-derived dendritic cells. J Invest Dermatol 120:233–238

    Article  PubMed  CAS  Google Scholar 

  20. Ryan CA, Gildea LA, Hulette BC, Dearman RJ, Kimber I, Gerberick GF (2004) Gene expression changes in peripheral blood-derived dendritic cells following exposure to a contact allergen. Toxicol Letters 150:301–316

    Article  CAS  Google Scholar 

  21. De Smedt ACA, Van Den Heuvel RL, Van Tendeloo VFI, Berneman ZN, Schoeters GER (2005) Capacity of CD34+ progenitor-derived dendritic cells to distinguish between sensitizers and irritants. Toxicol Lett 156:377–389

    Article  PubMed  CAS  Google Scholar 

  22. Boisleve F, Kerdine-Römer S, Pallardy M (2005) Implication of the MAPK pathways in the maturation of human dendritic cells induced by nickel and TNF-alpha. Toxicol 206:233–244

    Article  CAS  Google Scholar 

  23. Mizuashi M, Ohtani T, Nakagawa S, Aiba S (2005) Redox imbalance induced by contact sensitizers triggers the maturation of dendritic cells. J Invest Dermatol 124:579–586

    Article  PubMed  CAS  Google Scholar 

  24. Varona R, Villares R, Carramolino L, Goya I, Zaballos A, Gutiérrez J, Torres M, Martínez-A C, Márquez G (2001) CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses. J Clin Invest 107:R37–R45

    Article  PubMed  CAS  Google Scholar 

  25. Schmuth M, Neyer S, Rainer C, Grassegger A, Fritsch P, Romani N, Heufler C (2002) Expression of the C-C chemokine MIP-3 alpha/CCL20 in human epidermis with impaired permeability barrier function. Exp Dermatol 11:135–142

    Article  PubMed  CAS  Google Scholar 

  26. Schutyser E, Struyf S, Van Damme J (2003) The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth factor Rev 14:409–426

    Article  PubMed  CAS  Google Scholar 

  27. Wollenberg A, Mommaas M, Oppel T, Schottdorf EM, Gunther S, Moderer M (2002) Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases. J Invest Dermatol 118:327–334

    Article  PubMed  CAS  Google Scholar 

  28. Rustemeyer T, Preuss M, von Blomerg BME, Das PK, Scheper RJ (2003) Comparison of two in vitro dendritic cell maturation models for screening contact sensitizers using a panel of methacrylates. Exp Dermatol 12:682–691

    Article  PubMed  CAS  Google Scholar 

  29. Cruz MT, Gonçalo M, Figueiredo A, Carvalho AP, Duarte CB, Lopes MC (2002) Differential activation of nuclear factor kappa B subunits in a skin dendritic cell line in response to the strong sensitizer 2,4-dinitrofluourobenzene. Arch Dermatol Res 294:419–425

    PubMed  CAS  Google Scholar 

  30. Cruz MT, Gonçalo M, Figueiredo A, Carvalho AP, Duarte CB, Lopes MC (2004) Contact sensitizer nickel sulphate activates the transcription factors NF-kB and AP-1 and increases the expression of nitric oxide synthase in a skin dendritic cell line. Exp Dermatol 13:18–26

    Article  PubMed  CAS  Google Scholar 

  31. McColl SR (2002) Chemokines and dendritic cells: A crucial alliance. Immunol Cell Biol 80:489–496

    Article  PubMed  CAS  Google Scholar 

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Correspondence to MC Lopes.

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Cruz, M., Gonçalo, M., Paiva, A. et al. Contact sensitizers downregulate the expression of the chemokine receptors CCR6 and CXCR4 in a skin dendritic cell line. Arch Dermatol Res 297, 43–47 (2005). https://doi.org/10.1007/s00403-005-0574-8

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  • DOI: https://doi.org/10.1007/s00403-005-0574-8

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