The anti-psoriatic dimethylfumarate (DMF) has been anecdotically reported to reduce asthma symtoms and to improve quality of life of asthma patients. DMF decreases the expression of pro-inflammatory mediators by inhibiting the transcription factor nuclear factor B (NF-B) and might therefore be of interest for the therapy of inflammatory lung diseases. In this study we determined the effect of dimethylfumarate (DMF) on platelet derived growth factor (PDGF)-BB and tumor necrosis factor (TNF)- induced asthma relevant cytokines and NF-B activation by primary human asthmatic and non-asthmatic airway smooth muscle cells (ASMC). Methods: Confluent non-asthmatic and asthmatic ASMC were incubated with DMF (0.1-100 µM) and/or dexamethasone (0.0001-0.1 µM), NF-B p65 siRNA (100 nM), the NF-B inhibitor helenalin (1 µM) before stimulation with PDGF-BB or TNF- (10 ng/ml). Cytokine release was measured by enzyme linked immunosorbent assay. NF-B, MSK-1, and CREB activation was determined by immuno-blotting and EMSA. Results: TNF- induced eotaxin, RANTES and interleukin (IL)-6 as well as PDGF-BB induced IL-6 expression was inhibited by DMF and by dexamethasone from asthmatic and non-asthmatic ASMC, but the combination of both drugs showed no glucocorticoid sparing effect in either of the two groups. NF-B p65 siRNA and/or the NF-B inhibitor helenalin reduced PDGF-BB and TNF- induced cytokine expression, suggesting the involvement of NF-B signaling. DMF inhibited TNF- induced NF-B p65 phosphorylation, NF-B nuclear entry and NF-B -DNA complex formation, whereas PDGF-BB appeared not to activate NF-B within 60 min. Both stimuli induced the phosphorylation of mitogen and stress activated kinase (MSK)-1, NF-B p65 at Ser276, and CREB and all were inhibited by DMF. These data suggest that DMF down-regulates cytokine secretion not only by inhibiting NF-B but a wider range of NF-B linked signaling proteins which may explain its potential beneficial effect in asthma.