Modulation of IFNAR1 mRNA expression in multiple sclerosis patients.
Interferon-beta receptor (IFNAR) is composed of 2 subunits, IFNAR1 and IFNAR2, the latter of which is expressed as functional (IFNAR2.2), non-functional (IFNAR2.1) and soluble (IFNAR2.3) isoform. Real-Time PCR analysis of mRNA for all IFNAR components in multiple sclerosis patients naïve for therapy and undergoing long-term treatment with interferon-beta shows that IFNAR1 mRNA level is lower than in healthy controls. If long-term treated patients are divided according to the production of mRNA for Myxovirus protein-A, a marker of interferon-beta bioactivity, IFNAR1 mRNA reaches the values observed in controls only in Myxovirus protein-A-induced patients. Since chronic cell stimulation by interferon-beta induces IFNAR protein down-regulation, we suggest that the increase of IFNAR1 mRNA might serve as a mechanism for counterbalancing the loss of protein receptor, enhancing, at least in this sub-group of patients, cell responsiveness to interferon-beta.
Serana
Federico
F
Laboratorio di Biotecnologie, Diagnostic Department, Spedali Civili di Brescia, p.le Spedali Civili 1, 25123, Brescia, Italy.
Sottini
Alessandra
A
Ghidini
Claudia
C
Zanotti
Cinzia
C
Capra
Ruggero
R
Cordioli
Cinzia
C
Caimi
Luigi
L
Imberti
Luisa
L
D000328:Adult; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology* / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins; D009975:Orthomyxoviridae / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D064547:Myxovirus Resistance Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D019204:GTP-Binding Proteins