Ryutaro Matsumura

Effect of FK-506, a novel immunosuppressive drug on murine systemic lupus erythematosus

A novel immunosuppressive compound extracted from the fermentation broth of Streptomyces tsukubaensis belongs to the macrolide family. We gave this drug (FK-506) to MRL/lpr and NZB X NZW F1 (B/W F1) mice, an animal model of human systemic lupus erythematosus (SLE), to investigate its effect on the course of the disease. This drug showed potential to prolong the lifespan, to reduce proteinuria, and to prevent the progression of nephropathy. Appreciable differences in the levels of anti-dsDNA antibodies between treated and control animals were nil.

Alteration of circulating miRNAs in SSc: miR-30b regulates the expression of PDGF receptor β

OBJECTIVEnAlthough several miRNAs have been shown to regulate autoimmune pathogenesis by affecting lymphocyte function, the roles of miRNAs in the pathogenesis of SSc remain unclear. Therefore the purpose of this study was to identify miRNAs that play a role in the pathogenesis of SSc by quantitative PCR screening of serum miRNAs.nnnMETHODSnNinety-five miRNAs that were predicted to target SSc-related genes [IL-4, TGF-β, CTGF, PDGF-B, PDGF receptor (PDGFR) α/β and COL1A2) by in silico analyses were selected. The expression of these miRNAs in sera of SSc patients and healthy controls was measured by quantitative PCR. Involvement of miR-30b, which was most strongly down-regulated in SSc patients, in the regulation of PDGFR-β expression was examined by transfection experiments and 3-untranslated region (3-UTR) target luciferase assays. The expression of miR-30b in skin was evaluated in a bleomycin-induced dermal fibrosis model in mice and in SSc patients.nnnRESULTSnNineteen of 95 miRNAs were significantly decreased in the sera of SSc patients. Among them, miR-30b was most strongly down-regulated in SSc patients (P = 0.00006) and the levels of miR-30b were inversely correlated with modified Rodnan skin scores. Transfection of a miR-30b mimic repressed PDGFR-β expression in dermal fibroblasts and the activity of a luciferase reporter containing 3-UTR of PDGFR-β. Moreover, the expression of miR-30b was down-regulated in bleomycin-treated sclerotic skin and in affected skin in SSc patients.nnnCONCLUSIONnDown-regulation of miR-30b might be involved in the pathogenesis of SSc.

The immunosuppressant FK-506 prevents progression of diabetes in nonobese diabetic mice

A novel immunosuppressive compound, FK-506, isolated from Streptomyces has potent immunosuppressive activities. To investigate the effect of FK-506 on the course of diabetes in nonobese diabetic (NOD) mice, we gave this drug to these animals, from the age of 8 weeks, intraperitoneally, in doses of 0.1 mg (2.5 mg/kg/day) or 0.01 mg (0.25 mg/kg/day) three times a week. Overt diabetes were observed in 75.5% of control mice by the age of 20 weeks. In contrast, no diabetes occurred in mice given 0.1 mg of FK-506. Sixteen percent of mice treated with 0.01 mg of the drug became diabetic. Administration of this drug prevented the progression of insulitis in NOD mice. The mice given 0.1 mg of FK-506 lost weight, but this was reversible.