To advance the control of airway epithelial cell function and
asthma, we investigated the effects of a new
curcumin derivative,
CNB001, which possesses improved pharmacological properties. Normal human bronchial epithelial (NHBE) cells were stimulated with synthetic
double-stranded RNA,
Poly(I:C).
CNB001 significantly suppressed
IL-6, TNF-α, and
GM-CSF production by NHBE cells, and did so more effectively than did
curcumin or
dexamethasone (DEX).
CNB001 significantly inhibited the decrease of
E-cadherin mRNA expression and increase of
vimentin mRNA expression observed in NHBE cells induced by a combination of TGF-β1 and TNF-α, which are markers of
airway remodeling. In NHBE cells stimulated by TGF-β1,
CNB001 significantly downregulated the level of active
serine peptidase inhibitor clade E member (SERPINE) 1, which is also reported to be related to
airway remodeling. Whereas DEX alone significantly increased the active SERPINE1 level, the combination of DEX and
CNB001 significantly suppressed active SERPINE1. In addition,
CNB001 significantly suppressed neutrophil infiltration,
IL-6, TNF-α,
IL-13 and active SERPINE1 production in bronchoalveolar lavage fluid of the murine
asthma model, which was not observed in the case of DEX. In conclusion, the
curcumin derivative,
CNB001, is a promising candidate to treat
asthma associated with neutrophilic airway
inflammation and remodeling.