Increased expression of 2'5'oligoadenylate synthetase and double-stranded RNA dependent protein kinase messenger RNAs on affected skin of systemic sclerosis patients.
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, MxA, 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.
Coelho
Luiz Felipe Leomil
LF
Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
de Oliveira
Jaquelline Germano
JG
de Oliveira
Danilo Bretas
DB
Guedes
Antônio Carlos Martins
AC
Lanna
Cristina Costa Duarte
CC
Prados
Roberto Zimmer
RZ
Ferreira
Paulo César Peregrino
PC
Bonjardim
Cláudio Antônio
CA
Kroon
Erna Geessien
EG
D000227:Adenine Nucleotides / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects; D007372:Interferons / Q000009:adverse effects*; D008875:Middle Aged; D009843:Oligoribonucleotides / Q000378:metabolism; D011130:RNA Ligase (ATP) / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D012595:Scleroderma, Systemic / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000096:biosynthesis*
D000227:Adenine Nucleotides; D007370:Interferon Type I; D009843:Oligoribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C023505:2',5'-oligoadenylate; D007372:Interferons; D019892:eIF-2 Kinase; D011130:RNA Ligase (ATP)