Biswas, Chhanda; Chu, Niansheng; Burn, Thomas N.; Kreiger, Portia A.; Behrens, Edward M. published the artcile< Amelioration of Murine Macrophage Activation Syndrome by Monomethyl Fumarate in Both a Heme Oxygenase 1-Dependent and Heme Oxygenase 1-Independent Manner>, Product Details of C19H34O2, the main research area is macrophage activation syndrome monomethyl fumarate HO1.
Macrophage activation syndrome (MAS) is characterized by increased serum levels of ferritin and heme oxygenase 1 (HO-1), and yet no known function is ascribed to these mols. in MAS. Because HO-1 is antiinflammatory, we hypothesized that pharmacol. activation of HO-1 could ameliorate MAS disease activity. Di-Me fumarate (DMF), a treatment approved by the US Food and Drug Administration for multiple sclerosis, activates HO-1. Monomethyl fumarate (MMF) is the active metabolite of DMF. We therefore evaluated whether MMF could elicit HO-1-dependent therapeutic improvements in a murine model of MAS. We induced MAS by repeated activation of Toll-like receptor 9 (TLR-9) in wild-type and myeloid-specific HO-1-deficient mice. MMF was administered twice daily to test its efficacy. We assessed organ weights, serum cytokine levels, histol. features of the spleen and liver tissue, and complete blood cell counts to evaluate disease activity. Statistical testing was performed using Students t-test or by 2-way anal. of variance as appropriate. The presence of HO-1 was required for the majority of TLR-9-induced interleukin-10 (IL-10). IL-10 production in TLR-9-induced MAS was found to correlate with the myeloid-HO-1 gene dose in myeloid cells (P < 0.001). MMF treatment increased the levels of HO-1 in splenic macrophages by ∼2-fold (P < 0.01), increased serum levels of IL-10 in an HO-1-dependent manner in mice with TLR-9-induced MAS (P < 0.005), and improved multiple disease parameters in both an HO-1-dependent and HO-1-independent manner. TLR-9-induced production of IL-10 is regulated by HO-1 activity both in vitro and in vivo. Therapeutic enhancement of the HO-1/IL-10 axis in a murine model was able to significantly ameliorate MAS disease activity. These results suggest that HO-1 may be viable as a MAS therapeutic target, and treatment with DMF and MMF should be considered in future investigations of MAS therapy. Arthritis & Rheumatology published new progress about Anemia. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.
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