Review Article

Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?

Figure 3

Secretion of chemokines such as CXCL10, CCL11, or RANTES by ASMC attracts immune cells (eosinophils, T cells, or mast cells) into the asthmatic airway. In turn, these immune cells secrete proinflammatory cytokines (TNF-α, IFN-γ, etc.), which stimulate proinflammatory signaling molecules such as NF-κB or MSK-1 in ASMC, enhancing its proinflammatory function. DMF reduces intracellular reduced glutathione (GSH) level and thereby induces HO-1 expression and IκB-glutathionylation. DMF-induced HO-1 decreased CXCL10 and ASMC proliferation by an unknown mechanism. IκB-glutathionylation inhibited IκB degradation and subsequent NF-κB nuclear entry. Furthermore, DMF inhibited MSK-1-mediated histone H3 and NF-κB phosphorylation, leading to reduced secretion of CXCL10, CCL11, and RANTES. DMF reduces ASMC chemokine secretion and may therefore inhibit the crosstalk between ASMC and immune cells, leading to airway inflammation.
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