title: Anti-inflammatory effects of the petasin phyto drug Ze339 are mediated by inhibition of the STAT pathway.
abstract: Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB4in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers. To investigate the influence of viral and bacterial infections on the airways, HNECs were stimulated with viral mimics, bacterial toll-like-receptor (TLR)-ligands or cytokines, in presence or absence of Ze339. The study uncovers Ze339 modulated changes in pro-inflammatory mediators and decreased neutrophil chemotaxis as well as a reduction of the nuclear translocation and phosphorylation of STAT molecules. Taken together, this study suggests that phyto drug Ze339 specifically targets STAT-signalling pathways in HNECs and has high potential as a broad anti-inflammatory drug that exceeds current indication. © 2016 BioFactors, 43(3):388-399, 2017.
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Steiert
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Zissler
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.|Department of Otolaryngology and Head and Neck Surgery, TUM Medical School, Technical University of Munich, Munich, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Chaker
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Esser-von-Bieren
authors.affiliation: Chair and institute of environmental medicine, UNIKA-T, Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Augsburg, Germany.|CK CARE - Christine Kühne Center for allergy research and education, Davos, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dittlein
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Guerth
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Constanze A
authors.initials: CA
authors.lastname: Jakwerth
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, TUM Medical School, Technical University of Munich, Munich, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Piontek
authors.affiliation: Max Zeller Söhne AG, Romanshorn, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Zahner
authors.affiliation: Max Zeller Söhne AG, Romanshorn, Switzerland.
authors.forename: Juergen
authors.initials: J
authors.lastname: Drewe
authors.affiliation: Chair and institute of environmental medicine, UNIKA-T, Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Augsburg, Germany.|CK CARE - Christine Kühne Center for allergy research and education, Davos, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.affiliation: Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Schmidt-Weber
authors.affiliation: Chair and institute of environmental medicine, UNIKA-T, Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Augsburg, Germany.|CK CARE - Christine Kühne Center for allergy research and education, Davos, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gilles
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005408:Flagellin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D055666:Lipopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009296:Nasal Cavity / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D036901:Petasites / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011070:Poly I-C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D061251:Primary Cell Culture; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D018925:Chemokines; C508598:IL4 protein, human; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D010936:Plant Extracts; D050791:STAT Transcription Factors; D012717:Sesquiterpenes; C476335:Ze 339; D005408:Flagellin; D015847:Interleukin-4; D007371:Interferon-gamma; C418727:petasin; D011070:Poly I-C
keywords: STAT signalling; cytokines; human nasal epithelial cells; microbial patterns; petasin; viral inflammation