BACKGROUND: Thymic stromal lymphopoietin (TSLP) acts as a master switch for allergic inflammation and plays a key role in allergic diseases, including allergic rhinitis. Double-stranded RNA (dsRNA) recognized by Toll-like receptor 3 (TLR3) strongly activates TSLP release from human nasal epithelial cells (HNECs). Hop (Humulus lupulus L.) extracts have been shown to have potent pharmacologic effects on inflammation. METHODS: To investigate whether a hop water extract (HWE) prevents TSLP release from HNECs, human telomerase reverse transcriptase (hTERT)-transfected HNECs, used as a model of normal HNECs, were pretreated with HWE before treatment with the TLR3 ligand Polyinosine-polycytidylic acid (poly[I:C]). RESULTS: In the hTERT-transfected HNECs, treatment with HWE significantly reduced poly(I:C)-induced production and release of TSLP in a dose-dependent manner, as well as dexamethasone. Treatment with the protein kinase C (PKC) inhibitor GF109203X and NF-κB inhibitor IMD-0354 also reduced poly(I:C)-induced TSLP release from hTERT-transfected HNECs. Treatment with HWE efficiently prevented up-regulation of PKC activity by 12-O-tetradecanoyl phorbol-13-acetate but not NF-κB activity induced by IL-1β in hTERT-transfected HNECs. CONCLUSION: Our results clearly indicated that HWE inhibited dsRNA-induced production and release of TSLP via a PKC signal pathway in HNECs and it may have potent preventive effects against allergic rhinitis.
BACKGROUND:Thymic stromal lymphopoietin (TSLP) acts as a master switch for allergic inflammation and plays a key role in allergic diseases, including allergic rhinitis. Double-stranded RNA (dsRNA) recognized by Toll-like receptor 3 (TLR3) strongly activates TSLP release from human nasal epithelial cells (HNECs). Hop (Humulus lupulus L.) extracts have been shown to have potent pharmacologic effects on inflammation. METHODS: To investigate whether a hop water extract (HWE) prevents TSLP release from HNECs, human telomerase reverse transcriptase (hTERT)-transfected HNECs, used as a model of normal HNECs, were pretreated with HWE before treatment with the TLR3 ligand Polyinosine-polycytidylic acid (poly[I:C]). RESULTS: In the hTERT-transfected HNECs, treatment with HWE significantly reduced poly(I:C)-induced production and release of TSLP in a dose-dependent manner, as well as dexamethasone. Treatment with the protein kinase C (PKC) inhibitor GF109203X and NF-κB inhibitor IMD-0354 also reduced poly(I:C)-induced TSLP release from hTERT-transfected HNECs. Treatment with HWE efficiently prevented up-regulation of PKC activity by 12-O-tetradecanoyl phorbol-13-acetate but not NF-κB activity induced by IL-1β in hTERT-transfected HNECs. CONCLUSION: Our results clearly indicated that HWE inhibited dsRNA-induced production and release of TSLP via a PKC signal pathway in HNECs and it may have potent preventive effects against allergic rhinitis.
Authors: Geovanny F Perez; Krishna Pancham; Shehlanoor Huseni; Diego Preciado; Robert J Freishtat; Anamaris M Colberg-Poley; Eric P Hoffman; Mary C Rose; Gustavo Nino Journal: Eur Respir J Date: 2014-06-25 Impact factor: 16.671