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Effects of the Neuropeptides Substance P, Calcitonin Gene-Related Peptide and α-Melanocyte-Stimulating Hormone on the IL-8/IL-8 Receptor System in a Cultured Human Keratinocyte Cell Line and Dermal Fibroblasts

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Abstract

The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and α-melanocyte-stimulating hormone (α-MSH) are known to be able to regulate the production of cytokines in the skin. Since IL-8 plays an important role in cutaneous inflammation, the effects of SP, CGRP and α-MSH on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studied. Cultures of human dermal fibroblasts and an immortalized keratinocyte cell line HaCaT were treated with 10−8 M SP, CGRP or α-MSH. The results demonstrated that these neuropeptides have different effects on the IL-8 and IL-8RA expressions of the cells. SP and CGRP upregulated the IL-8RA mRNA expression in HaCaT cells, but had no influence on their IL-8 production, whereas, α-MSH had no effect on either the IL-8 or the IL-8RA mRNA expression in HaCaT cells. In contrast, α-MSH resulted in a time-dependent induction of the IL-8 mRNA expression in dermal fibroblasts. This induction was already detectable after 6 h, and after 12 h there was a 5-fold change in comparison with the controls. The IL-8 content of the supernatant was also increased, with a maximum at 48 h after α-MSH treatment. The data established in the present study support the notion that neuropeptides can directly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.

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REFERENCES

  1. Pincelli, C., F. Fantini, and A. Gianetti. 1993. Neuropeptides and skin inflammation. Dermatology 187:153-158.

    Google Scholar 

  2. Eedy, D. J. 1993. Neuropeptides in skin. Brit. J. Dermatol. 128:597-605.

    Google Scholar 

  3. Lotti, T., G. Hautmann, and E. Panconesi. Neuropeptides in skin. Clinical review. 1995. J. Am. Acad. Dermatol. 33:482-496.

    Google Scholar 

  4. Wallengren, J., R. Ekman, and F. Sundler. Occurrence and distribution of neuro-peptides in the human skin. 1987. Acta Dermato-Venereol. (Stockh) 67:185-192.

    Google Scholar 

  5. Slominski, A., J. Worstman, J. E. Mazurkiewicz, L. Matsuoka, J. Dietrich, K. Lawrence, A. Gorbani, and R. Paus. 1993. Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin. J. Lab. Clin. Med. 122:482-496.

    Google Scholar 

  6. Eedy, D. J., C. F. Johnston, C. Shaw, and K. D. Buchanan. 1991. Neuropeptides in psoriasis: An immunohistochemical and radioimmunoassay study. J. Invest. Dermatol. 96:434-438.

    Google Scholar 

  7. Gianetti, A., F. Fantini, A. Cimitan, and C. Pincelli. 1992. Vasoactive intestinal polypeptide and substance P in the pathogenesis of atopic dermatitis, Acta Dermato-Venereol. (Stockh) Suppl. 176:90-92.

    Google Scholar 

  8. Bull, H. A., J. Hothersall, N. Chowdhury, J. Cohen, and P. M. Dowd. 1996. Neuropeptides induce release of nitric oxide from human dermal microvascular endothelial cells. J. Invest. Dermatol. 106:655-660.

    Google Scholar 

  9. KemÉny, L., B. Restorff, G. Michel, and T. Ruzicka. 1994. Specific binding and lack of growth-promoting activity of substance P in cultured keratinocytes. J. Invest. Dermatol. 103:605-606.

    Google Scholar 

  10. Brown, J., P. Perrz, S. Hofeneider, and J. Ansel. 1990. Neuropeptide modulation of keratinocyte cytokine production. In: Oppenheim, Powanda, Kluger, Dinarello (Editors), Molecular and Cellular Biology of Cytokines. Wiley-Liss, Inc., pp. 451-456.

  11. Nilsson, J., A. von Euler, and C-J. Dalsgaard. 1985. Stimulation of connective tissue cell growth by substance P and substance K. Nature 315:61-65.

    Google Scholar 

  12. Ziche, M., L. Morbidelli, M. Pacini, P. Geppetti, and G. Alesandri. 1990. Substance P stimulated neovascularization in vivo and proliferation of cultured endothelial cells. Microvascular. Res. 40:264-266.

    Google Scholar 

  13. Naukkarinen, A., I. Harvima, K. Paukkonen, M-L. Aalto, and M. Horsmanheimo. 1993. Immunohistochemical analysis of sensory nerves and neuropeptides, and their contacts with mast cells in developing and mature psoriatic lesions. Arch. Derm. Res. 285:341-346.

    Google Scholar 

  14. Hosoi, J., G. F. Murphy, C. L. Egan, E. A. Lerner, S. Grabbe, A. Asahina, and R. D. Granstein. 1993. Regulation of Langerhans cell function by nerves containing calcitonin generalted peptide. Nature 363:159-163.

    Google Scholar 

  15. Slominski, A., R. Paus, and J. Mazurkiewicz. 1993. On the potential role of proopiomelanocortin in skin physiology and pathology. Mol. Cell. Endocrinol. 93:C1-C6.

    Google Scholar 

  16. Pears, J. S., R. T. Jung, W. Bartlett, M. C. K. Browning, K. Kenicer, and A. J. Thody. 1992. A case of hyperpigmentation due to α-MSH hypersecretion. Brit. J. Dermatol. 26:286-289.

    Google Scholar 

  17. Kock, A., E. Schauer, T. Schwarz, and T. Luger. 1990. MSH and ACTH production by human keratinocytes. A link between the neuronal and immune system. J. Invest. Dermatol. 94:543(A).

    Google Scholar 

  18. KemÉny, L., A. Sz. Kenderessy, E. Olasz, G. Michel, T. Ruzicka, and A. Dobozy. 1994. The interleukin-8 receptor: a potential target for antipsoriatic therapy. Eur. J. Pharmacol. 258:269-272.

    Google Scholar 

  19. Parenti, A., S. Amerini, F. Ledda, and C. A. Maggi. 1996. The tachykinin NK1 receptor mediates the migration-promoting effect of substance P on human skin fibroblasts in culture. Naunyn-Schmiedeberg Arch. Pharmacol. 353:475-481.

    Google Scholar 

  20. Proudfoot, A. E. I. 1998. The chemokine family. Potential therapeutic targets from allergy to HIV infection. Review. Eur. J. Dermatol. 8:147-157.

    Google Scholar 

  21. Fleischmajer, R., J. S. Perlish, T. Krieg, and R. Timpl. 1981. Variability in collagen and fibronectin synthesis by scleroderma fibroblasts in primary culture. J. Invest. Dermatol. 76:400-403.

    Google Scholar 

  22. Matsushima, K., and J. Oppenheim. 1989. Interleukin 8 and MCAF: Novel inflammatory cytokines inducible by IL-1 and TNF. Cytokine 1:2-12.

    Google Scholar 

  23. Holmes, W. E., J. Lee, W-J. Kuang, C. Rice, and W. I. Wood. 1991. Structure and functional expression of a human interleukin-8 receptor. Science 253:1278-1280.

    Google Scholar 

  24. Nakajima-Iijima, S., H. Hamada, P. Reddy, and T. Kakunaga. 1985. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc. Natl. Acad. Sci. U.S.A. 82:6133-6137.

    Google Scholar 

  25. Schoop, V. M., M. Mirancea, and N. E. Fusenig, 1999. Epidermal organization and differentiation of HaCaT keratinocytes in organotypic cocultures with human dermal fibroblasts. J. Invest. Dermatol. 112:545-555.

    Google Scholar 

  26. Viac, J., A. GuÉniche, J. D. Doutremepuich, U. Reichert, A. Claudy, and D. Schmitt. 1996. Substance P and keratinocyte activation markers: an in vitro approach. Arch. Dermatol. Res. 288:85-90.

    Google Scholar 

  27. Schulz, B., G. Michel, S. Wagner, R. SÜss, A. Beetz, R. U. Peter, L. KemÉny, and T. Ruzicka. 1993. Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro. J. Immunol. 151:4399-4406.

    Google Scholar 

  28. Weddel, G., H. A. Cowan, E. Palmer, and S. Ramaswamy. Psoriatic skin. 1965. Arch. Dermatol. 91:252-256.

    Google Scholar 

  29. Mohamadzadeh, M., M. Muller, T. Hultsch, A. Enk, J. Saloga, and J. Knop. 1994. Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants. Exp. Dermatol. 3:298-303.

    Google Scholar 

  30. Mauviel, A., S. Reitamo, A. Remitz, J. C. Lapiere, M. Ceska, M. Baggiolini, A. Walz, C. H. Evans, and J. Uitto. 1992. Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity. J. Immunol. 149:2969-2976.

    Google Scholar 

  31. Kiss, M., M. Wlaschek, P. Brenneisen, G. Michel, C. Hommel, T. S. Lange, D. Peus, L. KemÉny, A. Dobozy, K. Scharffetter-Kochanek, and T. Ruzicka. 1995. α-Melanocyte stimulating hormone induces collagenase-matrix-metalloproteinase-1 in human dermal fibroblasts. Biol. Chem. Hoppe-Seyler 376:425-430.

    Google Scholar 

  32. Unemori, E. N., E. P. Amento, E. A. Bauer, and R. Horuk. 1993. Melanoma growth-promoting activity/GRO decreases collagen expression by human fibroblasts. Regulation by C-X-C but not C-C cytokines. J. Biol. Chem. 268:1138-1342.

    Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, Albert Szent-Györgyi Medical University, H-6701, Szeged, P.O. Box 480, Hungary

    Mária Kiss, Lajos Kemény, Rolland Gyulai, Sándor Husz, Réka Kovács & Attila Dobozy

  2. Department of Dermatology, Heinrich-Heine-University of Düsseldorf, D-40225, Moorenstr. 5, Düsseldorf, Germany

    Günter Michel & Thomas Ruzicka

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  1. Mária Kiss
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  2. Lajos Kemény
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  3. Rolland Gyulai
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  4. Günter Michel
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  7. Attila Dobozy
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  8. Thomas Ruzicka
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Kiss, M., Kemény, L., Gyulai, R. et al. Effects of the Neuropeptides Substance P, Calcitonin Gene-Related Peptide and α-Melanocyte-Stimulating Hormone on the IL-8/IL-8 Receptor System in a Cultured Human Keratinocyte Cell Line and Dermal Fibroblasts. Inflammation 23, 557–567 (1999). https://doi.org/10.1023/A:1020294507767

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