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Amygdalin Analogues Inhibit IFN-γ Signalling and Reduce the Inflammatory Response in Human Epidermal Keratinocytes

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Abstract

Peptide T (PT), an octapeptide fragment located in the V2 region of the HIV-1 gp120-coating protein, appears to be beneficial in the treatment of psoriasis. Our previous investigations suggest that keratinocytes play a key role in conditioning the therapeutic effects of PT in psoriasis. The aim of this study was to explore the effects of PT and the peptidomimetic natural products, Dhurrin and Prunasin, on the expression of the IL-6, IL-8, IL-23, HSP70 and ICAM-1 on IFN-γ and TNF-α-NHEK activated cells. Moreover, we analysed the interference of PT and its analogues through STAT-3 activation. Our results show that the analogues tested exhibit the beneficial biological effects of PT, suggesting the primary role of keratinocytes upon which PT and the peptidomimetics act directly, by reducing proinflammatory responses. Its reduction appears to be important for therapeutic approach in psoriasis pathogenesis.

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References

  1. Pert, C.B., and M.R. Ruff. 1986. Peptide t[4–8]: a pentapeptide sequence in the aids virus envelope which blocks infectivity is essentially conserved across nine isolates. Clinical Neuropharmacology 9(4): 482–484.

    PubMed  Google Scholar 

  2. Yang, T.C., J. Rendell, W. Gulliverb, and V. Bootha. 2009. Peptide T exhibits a well-defined structure in fluorinated solvent at low temperature. Journal of Peptide Science 15: 818–823.

    Article  PubMed  CAS  Google Scholar 

  3. Marcusson, J.A., D. Lazega, C.B. Pert, M.R. Ruff, K.G. Sundquist, and L. Wetterberg. 1989. Peptide T and psoriasis. Acta Dermato Venereol Supplement (Stockh) 146: 117–121.

    CAS  Google Scholar 

  4. Raychaudhuri, S.K., S.P. Raychaudhuri, and E.M. Farber. 1998. Anti-chemotactic activities of peptide-T: a possible mechanism of actions for its therapeutic effects on psoriasis. International Journal of Immunopharmacology 20(11): 661–667.

    Article  PubMed  CAS  Google Scholar 

  5. Baroni, A., I. Paoletti, R. Greco, R.A. Satriano, E. Ruocco, M.A. Tufano, et al. 2005. Immunomodulatory effects of a set of amygdalin analogues on human keratinocytes cells. Experimental Dermatology 14(11): 854–859.

    Article  PubMed  CAS  Google Scholar 

  6. Tufano, M.A., R. Greco, I. Paoletti, G. Donnarumma, N. Canozo, and A. Baroni. 2002. Immunomodulatory effects of peptide T on human keratinocyte cells. The British Journal of Dermatology 147(4): 663–669.

    Article  PubMed  CAS  Google Scholar 

  7. Tohyama, M., Y. Hanakawa, Y. Shirakata, et al. 2009. IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression. European Journal of Immunology 39: 2779–2788.

    Article  PubMed  CAS  Google Scholar 

  8. Barna, M., F.G. Snijdewint, F.L. van der Heijden, J.D. Bos, and M.L. Kapsenberg. 1994. Characterization of lesional psoriatic skin T lymphocyte clones. Acta Derm Venereol Suppl (Stockh) 186: 9–11.

    CAS  Google Scholar 

  9. Albanesi, C., C. Scarponi, S. Sebastiani, A. Cavani, M. Federici, S. Sozzani, et al. 2001. A cytokine-to-chemokine axis between T lymphocytes and keratinocytes can favor Th1 cell accumulation in chronic inflammatory skin diseases. Journal of Leukocyte Biology 70(4): 617–623.

    PubMed  CAS  Google Scholar 

  10. Federici, M., M.L. Giustizieri, C. Scarponi, G. Girolomoni, and C. Albanesi. 2002. Impaired IFN-γ-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1. The Journal of Immunology 169: 434–442.

    PubMed  CAS  Google Scholar 

  11. Hongqin, T., L. Xinyu, G. Heng, X. Lanfang, W. Yongfang, and S. Shasha. 2011. Triptolide inhibits IFN-γ signaling via the Jak/STAT. Pathway in HaCat keratinocytes. Phytotherapy Research 25: 1678–1685.

    Article  PubMed  Google Scholar 

  12. Wegenka, U.M., C. Lütticken, J. Buschmann, et al. 1994. The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family. Molecular and Cellular Biology 14(5): 3186–3196.

    PubMed  CAS  Google Scholar 

  13. Zhong, Z., Z. Wen, and J.E. Darnell Jr. 1994. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264(5155): 95–98.

    Article  PubMed  CAS  Google Scholar 

  14. Caldenhoven, E., T. van Dijk, J.A. Raaijmakers, J.W. Lammers, L. Koenderman, and R.P. De Groot. 1995. Activation of the STAT3/acute phase response factor transcription factor by interleukin-5. The Journal of Biological Chemistry 270(43): 25778–25784.

    Article  PubMed  CAS  Google Scholar 

  15. Miyoshi, K., M. Takaishi, K. Nakajima, et al. 2011. Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. The Journal of Investigative Dermatology 131(1): 108–117.

    Article  PubMed  CAS  Google Scholar 

  16. Wen, Z., Z. Zhong, and J.E.J. Darnell. 1995. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82: 241–250.

    Article  PubMed  CAS  Google Scholar 

  17. Yuan, Z.L., Y.J. Guan, D. Chatterjee, and Y.E. Chin. 2005. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 307: 269–273.

    Article  PubMed  CAS  Google Scholar 

  18. Sestito, R., S. Madonna, C. Scarponi, et al. 2011. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. The FASEB Journal Research Communication 25(3): 916–927.

    Article  CAS  Google Scholar 

  19. Wang, D., B. Eiz-Vesper, J. Zeitvogel, R. Dressel, T. Werfel, and M. Wittmann. 2011. Human keratinocytes release high levels of inducible heat shock protein 70 that enhances peptide uptake. Experimental Dermatology 20(8): 637–641.

    Article  PubMed  CAS  Google Scholar 

  20. Curry, J.L., J.Z. Qin, B. Bonish, R. Carrick, P. Bacon, J. Panella, et al. 2003. Innate immune-related receptors in normal and psoriatic skin. Archives of Pathology & Laboratory Medicine 127(2): 178–186.

    CAS  Google Scholar 

  21. Boyman, O., C. Conrad, C. Dudli, E. Kielhorn, B.J. Nickoloff, and F.O. Nestle. 2005. Activation of dendritic antigen-presenting cells expressing common heat shock protein receptor CD91 during induction of psoriasis. The British Journal of Dermatology 152(6): 1211–1218.

    Article  PubMed  CAS  Google Scholar 

  22. Fang, S., F. Zeng, and Q. Guo. 2008. Comparative proteomics analysis of cytokeratin and involucrin expression in lesions from patients with systemic lupus erythematosus. Acta Biochimica et Biophysica Sinica 40(12): 989–995.

    Article  PubMed  CAS  Google Scholar 

  23. Pockley, A.G., M. Muthana, and S.K. Calderwood. 2008. The dual immunoregulatory roles of stress proteins. Trends in Biochemical Sciences 33(2): 71–79.

    Article  PubMed  CAS  Google Scholar 

  24. Chan, J.R., W. Blumenschein, E. Murphy, et al. 2006. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. The Journal of Experimental Medicine 203: 2577–2587.

    Article  PubMed  CAS  Google Scholar 

  25. Reddy, M., C. Davis, J. Wong, P. Marsters, C. Pendley, and U. Prabhakar. 2007. Modulation of CLA, IL-12R, CD40L, and IL-2Ra expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275. Cellular Immunology 247: 1–11.

    Article  PubMed  CAS  Google Scholar 

  26. Tang, C., S. Chen, H. Qian, and W. Huang. 2012. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology 135(2): 112–124.

    Article  PubMed  CAS  Google Scholar 

  27. Kanda, N., and S. Watanabe. 2008. IL-12, IL-23, and IL-27 enhance human beta-defensin-2 production in human keratinocytes. European Journal of Immunology 38(5): 1287–1296.

    Article  PubMed  CAS  Google Scholar 

  28. Kanai, Y., T. Satoh, K. Igawa, and H. Yokozeki. 2012. Impaired expression of Tim-3 on Th17 and Th1 cells in psoriasis. Acta Derm Venereol Suppl (Stockh) 92: 367–371.

    Article  CAS  Google Scholar 

  29. Parham, C., M. Chirica, J. Timans, et al. 2002. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. The Journal of Immunology 168: 5699–5708.

    PubMed  CAS  Google Scholar 

  30. Coimbra, S., A. Figueiredo, E. Castro, P. Rocha-Pereira, and A. Santos-Silva. 2012. The roles of cells and cytokines in the pathogenesis of psoriasis. International Journal of Dermatology 51(4): 389–395.

    Article  PubMed  CAS  Google Scholar 

  31. Tonel, G., C. Conrad, U. Laggner, et al. 2010. Cutting edge: a critical functional role for IL-23 in psoriasis. The Journal of Immunology 185: 5688–5691.

    Article  PubMed  CAS  Google Scholar 

  32. Victor, F.C., and A.B. Gottlieb. 2002. TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis. Journal of Drugs in Dermatology 1(3): 264–275.

    PubMed  Google Scholar 

  33. Bito, T., Roy, S., Sen, C.K., Packer L. 2000. Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radical Biology and Medicine 28(2):219–27

    Google Scholar 

  34. Jarvis, M., Marzolini, M., Wang, X.N., Jackson, G., Sviland, L., Dickinson, A.M. 2003. Heat shock protein 70: correlation of expression with degree of graft-versus-host response and clinical graft-versus-host disease. Transplantation 76(5):849–53

    Google Scholar 

  35. Novota, P., L. Sviland, S. Zinöcker, P. Stocki, Y. Balavarca, H. Bickeböller, et al. 2008. Correlation of Hsp70-1 and Hsp70-2 gene expression with the degree of graft-versus-host reaction in a rat skin explant model. Transplantation 85(12): 1809–1816.

    Article  PubMed  CAS  Google Scholar 

  36. Baroni, A., I. Paoletti, E. Ruocco, M. Agozzino, M.A. Tufano, and G. Donnarumma. 2004. Possible role of Malassezia furfur in psoriasis: modulation of TGF-beta1, integrin, and HSP70 expression in human keratinocytes and in the skin of psoriasis-affected patients. Journal of Cutaneous Pathology 31(1): 35–42.

    Article  PubMed  Google Scholar 

  37. Bayramgürler, D., S.K. Ozkara, R. Apaydin, C. Erçin, and N. Bilen. 2004. Heat shock proteins 60 and 70 expression of cutaneous lichen planus: comparison with normal skin and psoriasis vulgaris. Journal of Cutaneous Pathology 31(9): 586–594.

    Article  PubMed  Google Scholar 

  38. Ghoreishi, M., I. Katayama, H. Yokozeki, and K. Nishioka. 1993. Analysis of 70 KD heat shock protein (HSP70) expression in the lesional skin of lupus erythematosus (LE) and LE related diseases. The Journal of Dermatology 20(7): 400–405.

    PubMed  CAS  Google Scholar 

  39. Villalobos-Hurtado, R., S.H. Sánchez-Rogriguez, E. Avalos-Díaz, and R. Herrera-Esparza. 2003. Possible role of Hsp70 in autoantigen shuttling to the dermo-epidermal junction in systemic lupus erythematosus. Reumatismo 55(3): 155–158.

    PubMed  CAS  Google Scholar 

  40. Yokozeki, H., Ghoreishi, M., Takagawa, S., Takayama, K., Satoh, T., Katayama, I., Takeda, K., Akira, S., Nishioka, K. 2000. Signal transducer and activator of transcription 6 is essential in the induction of contact hypersensitivity. Journal of Experimental Medicine 191(6):995–1004

    Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, Second University of Naples, Naples, Italy

    Adone Baroni

  2. Department d’Enginyeria Quimica (UPC), ETSEIB, Barcelona, Spain

    Juan Jesus Perez

  3. Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Via Costantinopoli, 16, 80100, Napoli, Italy

    Iole Paoletti, Vincenza De Gregorio, Maria Antonietta Tufano & Giovanna Donnarumma

Authors
  1. Iole Paoletti
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  2. Vincenza De Gregorio
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  3. Adone Baroni
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  4. Maria Antonietta Tufano
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  5. Giovanna Donnarumma
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  6. Juan Jesus Perez
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Corresponding author

Correspondence to Maria Antonietta Tufano.

Additional information

The first two authors Iole Paoletti and Vincenza De Gregorio equally contributed to this work.

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Paoletti, I., De Gregorio, V., Baroni, A. et al. Amygdalin Analogues Inhibit IFN-γ Signalling and Reduce the Inflammatory Response in Human Epidermal Keratinocytes. Inflammation 36, 1316–1326 (2013). https://doi.org/10.1007/s10753-013-9670-7

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  • DOI: https://doi.org/10.1007/s10753-013-9670-7

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