Background and aims Scleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatologic autoimmune disease characterised by skin, internal organs and blood vessels, and there is no effective therapy. The purposes of current study are to develop a model of GvHD-induced scleroderma that more fully represents human condition, and to investigate the effects of 5-aminolevulinic acid (5-ALA), an intermediate of heme synthesis, enhance HO-1 activity to cleave heme to form biliverdin, CO, and iron on this model.
Methods Scl-GvHD was induced by injection of lymphocytes from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination activating gene 2 null mice).
Results We successfully established an scl-GvHD model, which is similar to the human disease particularly in the skin, progressive inflammation and fibrosis of internal organs including lung, kidney, and liver. We found that treatment with 5-ALA and iron (Fe2+) significantly reduced progressive inflammation and fibrosis in the skin and ear. Furthermore, by quantitative real-time PCR analysis, 5-ALA and Fe2+ suppressed the inflammatory cytokines and TGF-β, type I collagen mRNAs expression. These results indicate that combination treatment with 5-ALA and Fe2+ exhibited a protective effect on tissue fibrosis and inflammation of scl-GvHD model mice.
Conclusions The model of GvHD-induced SSc has shown most of symptoms of human disease and is likely to contribute to better understanding of the disease mechanism. Furthermore, efficacy of the 5-ALA has important implication for clarifying the mechanism of HO-1 activity in autoimmune diseases, and may provide a favourable opportunity for clinical therapy.
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