Skip to main content

Advertisement

SpringerLink
Log in

Increased expression of 2′5′oligoadenylate synthetase and double-stranded RNA dependent protein kinase messenger RNAs on affected skin of systemic sclerosis patients

  • Short Communication
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Scleroderma or systemic sclerosis (SSc) is an autoimmune disorder of unknown aetiology characterized by excessive collagen synthesis and subsequent deposition on the skin and various internal organs. Interferons (IFNs) are well-known immunomodulators and inhibitors of collagen production. However, IFN therapy has been implicated in the development or exacerbation of several autoimmune diseases, including SSc. We analyzed the expression of several interferon-stimulated genes (ISGs) in affected skin of SSc patients (skin tissue and cultured skin fibroblasts). A set of ISGs (PKR, 2′5′OAS, M×A, and 6–16) was analyzed by real-time PCR using RNA extracted from cultured skin fibroblasts and skin tissue of normal individuals and SSc patients. Both normal and SSc affected skin cultured fibroblasts were sensitive to the IFN treatment and presented similar levels of all ISGs tested. However, PKR and 2′5′OAS mRNA expression levels were significantly higher in the affected skin tissue of SSc patients when compared to normal controls. These data suggest that the IFN system plays a role in the pathogenesis of SSc.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Abu-Shakra M, Sukenik S, Buskila D (2000) Systemic sclerosis: another rheumatic disease associated with hepatitis C virus infection. Clin Rheumatol 19:378–380

    Article  PubMed  CAS  Google Scholar 

  2. Baccala R, Kono DH, Theofilopoulos AN (2005) Interferons as pathogenic effectors in autoimmunity. Immunol Rev 204:9–26

    Article  PubMed  CAS  Google Scholar 

  3. Banchereau J, Pascual V, Palucka AK (2004) Autoimmunity through cytokine-induced dendritic cell activation. Immunity 20:539–550

    Article  PubMed  CAS  Google Scholar 

  4. Beretta L, Caronni M, Vanoli M et al (2002) Systemic sclerosis after interferon-alfa therapy for myeloproliferative disorders. Br J Dermatol 147:385–386

    Article  PubMed  CAS  Google Scholar 

  5. Bonjardim CA. (2005) Interferons (IFNs) are key cytokines in both innate and adaptive antiviral immune responses—and viruses counteract IFN action. Microbes Infect 7:569–578

    Article  PubMed  CAS  Google Scholar 

  6. Carvalho AF, Santos JR, Gentz R, Bonjardim CA, Golgher RR, Ferreira PC, Kroon EG (1998) Culture of human amniotic cells: a system to study interferon production. Placenta 19:307–314

    Article  PubMed  CAS  Google Scholar 

  7. Chawla-Sarkar M, Lindner DJ, Liu YF et al (2003) Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis 8:237–49

    Article  PubMed  CAS  Google Scholar 

  8. Denton CP, Black CM (2004) Scleroderma-clinical and pathological advances. Best Pract Res Clin Rheumatol 18:271–290

    PubMed  CAS  Google Scholar 

  9. de Veer MJ, Holko M, Frevel M et al (2001) Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 69:912–920

    PubMed  Google Scholar 

  10. Giacomelli R, Cipriani P, Fulminis A et al (2001) Circulating gamma/delta T lymphocytes from systemic sclerosis (SSc) patients display a T helper (Th) 1 polarization. Clin Exp Immunol 125:310–315

    Article  PubMed  CAS  Google Scholar 

  11. Harris ML, Rosen A (2003) Autoimmunity in scleroderma: the origin, pathogenetic role, clinical significance of autoantibodies. Curr Opin Rheumatol 15:778–784

    Article  PubMed  CAS  Google Scholar 

  12. Jimenez SA, Derk CT (2004) Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med 140:37–50

    PubMed  CAS  Google Scholar 

  13. Kontsek P, Karayianni-Vasconcelos G, Kontsekova E (2003) The human interferon system: characterization and classification after discovery of novel members. Acta Virol 47:201–215

    PubMed  CAS  Google Scholar 

  14. Oliveira JG, Prados RZ, Guedes AC et al (1999) The housekeeping gene glyceraldehyde-3-phosphate dehydrogenase is inappropriate as internal control in comparative studies between skin tissue and cultured skin fibroblasts using Northern blot analysis. Arch Dermatol Res 291:659–661

    Article  PubMed  CAS  Google Scholar 

  15. Solans R, Bosch JA, Esteban I et al (2004) Systemic sclerosis developing in association with the use of interferon alpha therapy for chronic viral hepatitis. Clin Exp Rheumatol 22:625–628

    PubMed  CAS  Google Scholar 

  16. Stark GR, Kerr IM, Williams BR et al (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264

    Article  PubMed  CAS  Google Scholar 

  17. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic, Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis. Arthritis Rheum 23:581–590

    Article  Google Scholar 

  18. Tan FK, Zhou X, Mayes MD et al (2006) Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients. Rheumatology 45:694–702

    Article  PubMed  CAS  Google Scholar 

  19. Theofilopoulos AN, Baccala R, Beutler B et al (2005) Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 23:307–336

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Angela S. Lopes, Daniela Lemos, João Rodrigues dos Santos, Ilda M. V. Gama and Maria A. Souza for their secretarial/technical assistance. We also thank Dr. Gilles Uzé for help on quantitative real time PCR experiments. This work was supported by research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG).

Author information

Author notes

  1. Luiz Felipe Leomil Coelho

    Present address: Laboratório de Microbiologia, Departamento de Parasitologia e Microbiologia, Centro de Ciências da Saúde, Universidade Federal do Piauí, Teresina, Piauí, Brazil

Authors and Affiliations

  1. Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, CEP: 31270-910, Caixa Postal 486, Belo Horizonte, Minas Gerais, Brazil

    Luiz Felipe Leomil Coelho, Jaquelline Germano de Oliveira, Danilo Bretas de Oliveira, Paulo César Peregrino Ferreira, Cláudio Antônio Bonjardim & Erna Geessien Kroon

  2. Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Antônio Carlos Martins Guedes & Cristina Costa Duarte Lanna

  3. Departamento de Cirurgia Plástica, Hospital da Baleia, Fundação Benjamin Guimarães, Belo Horizonte, Minas Gerais, Brazil

    Roberto Zimmer Prados

Authors
  1. Luiz Felipe Leomil Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jaquelline Germano de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danilo Bretas de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antônio Carlos Martins Guedes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cristina Costa Duarte Lanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roberto Zimmer Prados
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paulo César Peregrino Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cláudio Antônio Bonjardim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Erna Geessien Kroon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erna Geessien Kroon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coelho, L.F.L., de Oliveira, J., de Oliveira, D.B. et al. Increased expression of 2′5′oligoadenylate synthetase and double-stranded RNA dependent protein kinase messenger RNAs on affected skin of systemic sclerosis patients. Arch Dermatol Res 299, 259–262 (2007). https://doi.org/10.1007/s00403-007-0737-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-007-0737-x

Keywords

Search

Navigation