Abstract Interferon-β (IFN-β) ameliorates disease course in a subset of patients with MS. The reasons for heterogeneity of clinical responses, however, are unclear. We assessed possible effects of IFN-β on the gene expression of the leukocyte adhesion molecules VLA-4 and LFA-1 during the first year of treatment of 50 patients with relapsing–remitting MS who showed differential clinical responses. We observed a significant reduction of VLA-4 (P=0.002) and LFA-1 (P=0.03) mRNA expression compared to baseline in first-year clinical responders (n=22). In contrast, first-year IFN-β non-responders (n=28) had unchanged levels of VLA-4 and LFA-1. In vitro treatment of PBMC with IFN-β indicated a direct effect on transcription of the integrins' genes. Transcriptional downmodulation of adhesion molecules during IFN-β treatment may contribute to its mode of action in MS. Keywords Multiple sclerosis; Interferon-β; Adhesion molecules; VLA-4; LFA-1 Abbreviations BBB, blood–brain barrier; IFN-β, interferon-β; FACS, fluorescence-activated cell sorting; FITC, fluorescein-iso-thiocyanate; LFA-1, leukocyte functional antigen-1; MS, multiple sclerosis; PBMC, peripheral blood mononuclear cells; PE, phycoerithrin; PE-Cy5, phycoerithrin-cyanin 5; RR-MS, relapsing-remitting multiple sclerosis; RM-ANOVA, repeated measures analysis of variance; RT-PCR, reverse transcriptase PCR; VLA-4, very late antigen 4
Decreased integrin gene expression in patients with MS responding to interferon-beta treatment.
BONANNI, Laura;
2004-01-01
Abstract
Abstract Interferon-β (IFN-β) ameliorates disease course in a subset of patients with MS. The reasons for heterogeneity of clinical responses, however, are unclear. We assessed possible effects of IFN-β on the gene expression of the leukocyte adhesion molecules VLA-4 and LFA-1 during the first year of treatment of 50 patients with relapsing–remitting MS who showed differential clinical responses. We observed a significant reduction of VLA-4 (P=0.002) and LFA-1 (P=0.03) mRNA expression compared to baseline in first-year clinical responders (n=22). In contrast, first-year IFN-β non-responders (n=28) had unchanged levels of VLA-4 and LFA-1. In vitro treatment of PBMC with IFN-β indicated a direct effect on transcription of the integrins' genes. Transcriptional downmodulation of adhesion molecules during IFN-β treatment may contribute to its mode of action in MS. Keywords Multiple sclerosis; Interferon-β; Adhesion molecules; VLA-4; LFA-1 Abbreviations BBB, blood–brain barrier; IFN-β, interferon-β; FACS, fluorescence-activated cell sorting; FITC, fluorescein-iso-thiocyanate; LFA-1, leukocyte functional antigen-1; MS, multiple sclerosis; PBMC, peripheral blood mononuclear cells; PE, phycoerithrin; PE-Cy5, phycoerithrin-cyanin 5; RR-MS, relapsing-remitting multiple sclerosis; RM-ANOVA, repeated measures analysis of variance; RT-PCR, reverse transcriptase PCR; VLA-4, very late antigen 4I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
