Dehydrocostus lactone, a sesquiterpene from Saussurea lappa Clarke, suppresses allergic airway inflammation by binding to dimerized translationally controlled tumor protein.

ABSTRACT

BACKGROUND: We previously reported that the biologically active form of histamine releasing factor (HRF) is dimerized translationally controlled tumor protein (dTCTP) which is involved in a number of allergic diseases. HYPOTHESIS/PURPOSE: Hoping that agents that modulate dTCTP may provide new therapeutic targets to allergic inflammatory diseases, we screened a library of natural products for substances that inhibit dTCTP. One such inhibitor we found was dehydrocostus lactone (DCL), a natural sesquiterpene present in rhizome of Saussurea lappa Clarke, the subject of this study. METHODS: We evaluated the therapeutic efficacy of DCL in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation, employing the ELISA system using BEAS-2B cells and splenocytes, and confirmed that DCL interacts with dTCTP using SPR assay. RESULTS: DCL inhibited dTCTP-induced secretion of IL-8 in BEAS-2B cells. From kinetic analysis of dTCTP and DCL, we found that KD value was 5.33 ±â€¯0.03 µM between dTCTP and DCL. DCL also significantly reduced inflammatory lung eosinophilia, type 2 cytokines in BALF, as well as OVA specific IgE and mucus production in a mouse model of ovalbumin induced allergy. Moreover, DCL suppressed NF-κB activation. CONCLUSION: DCL's therapeutic potential in allergic airway inflammation is based on its anti-inflammatory activity of suppressing the function of dTCTP.