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.
References
Abu-Shakra M, Sukenik S, Buskila D (2000) Systemic sclerosis: another rheumatic disease associated with hepatitis C virus infection. Clin Rheumatol 19:378–380
Baccala R, Kono DH, Theofilopoulos AN (2005) Interferons as pathogenic effectors in autoimmunity. Immunol Rev 204:9–26
Banchereau J, Pascual V, Palucka AK (2004) Autoimmunity through cytokine-induced dendritic cell activation. Immunity 20:539–550
Beretta L, Caronni M, Vanoli M et al (2002) Systemic sclerosis after interferon-alfa therapy for myeloproliferative disorders. Br J Dermatol 147:385–386
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
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
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
Denton CP, Black CM (2004) Scleroderma-clinical and pathological advances. Best Pract Res Clin Rheumatol 18:271–290
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
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
Harris ML, Rosen A (2003) Autoimmunity in scleroderma: the origin, pathogenetic role, clinical significance of autoantibodies. Curr Opin Rheumatol 15:778–784
Jimenez SA, Derk CT (2004) Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med 140:37–50
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
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
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
Stark GR, Kerr IM, Williams BR et al (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264
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
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
Theofilopoulos AN, Baccala R, Beutler B et al (2005) Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 23:307–336
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
Authors and Affiliations
Corresponding author
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-007-0737-x