Matches in SemOpenAlex for { <https://semopenalex.org/work/W2897502407> ?p ?o ?g. }
- W2897502407 endingPage "L1057" @default.
- W2897502407 startingPage "L1042" @default.
- W2897502407 abstract "Alternaria alternata is a fungal allergen associated with severe asthma and asthma exacerbations. Similarly to other asthma-associated allergens, Alternaria secretes a serine-like trypsin protease(s) that is thought to act through the G protein-coupled receptor protease-activated receptor-2 (PAR2) to induce asthma symptoms. However, specific mechanisms underlying Alternaria-induced PAR2 activation and signaling remain ill-defined. We sought to determine whether Alternaria-induced PAR2 signaling contributed to asthma symptoms via a PAR2/β-arrestin signaling axis, identify the protease activity responsible for PAR2 signaling, and determine whether protease activity was sufficient for Alternaria-induced asthma symptoms in animal models. We initially used in vitro models to demonstrate Alternaria-induced PAR2/β-arrestin-2 signaling. Alternaria filtrates were then used to sensitize and challenge wild-type, PAR2-/- and β-arrestin-2-/- mice in vivo. Intranasal administration of Alternaria filtrate resulted in a protease-dependent increase of airway inflammation and mucin production in wild-type but not PAR2-/- or β-arrestin-2-/- mice. Protease was isolated from Alternaria preparations, and select in vitro and in vivo experiments were repeated to evaluate sufficiency of the isolated Alternaria protease to induce asthma phenotype. Administration of a single isolated serine protease from Alternaria, Alternaria alkaline serine protease (AASP), was sufficient to fully activate PAR2 signaling and induce β-arrestin-2-/--dependent eosinophil and lymphocyte recruitment in vivo. In conclusion, Alternaria filtrates induce airway inflammation and mucus hyperplasia largely via AASP using the PAR2/β-arrestin signaling axis. Thus, β-arrestin-biased PAR2 antagonists represent novel therapeutic targets for treating aeroallergen-induced asthma." @default.
- W2897502407 created "2018-10-26" @default.
- W2897502407 creator A5006730507 @default.
- W2897502407 creator A5012818050 @default.
- W2897502407 creator A5027280879 @default.
- W2897502407 creator A5031150262 @default.
- W2897502407 creator A5037411659 @default.
- W2897502407 creator A5038451412 @default.
- W2897502407 creator A5040234468 @default.
- W2897502407 creator A5045627202 @default.
- W2897502407 creator A5053292820 @default.
- W2897502407 creator A5074102047 @default.
- W2897502407 creator A5077297886 @default.
- W2897502407 date "2018-12-01" @default.
- W2897502407 modified "2023-10-14" @default.
- W2897502407 title "Protease-activated receptor-2 signaling through β-arrestin-2 mediates <i>Alternaria</i> alkaline serine protease-induced airway inflammation" @default.
- W2897502407 cites W1566514487 @default.
- W2897502407 cites W1656256413 @default.
- W2897502407 cites W1811719059 @default.
- W2897502407 cites W1827703464 @default.
- W2897502407 cites W1854396704 @default.
- W2897502407 cites W1955447442 @default.
- W2897502407 cites W1962209258 @default.
- W2897502407 cites W1969235413 @default.
- W2897502407 cites W1977649999 @default.
- W2897502407 cites W1979580827 @default.
- W2897502407 cites W1989431047 @default.
- W2897502407 cites W1992045794 @default.
- W2897502407 cites W1997495128 @default.
- W2897502407 cites W2000517447 @default.
- W2897502407 cites W2001893139 @default.
- W2897502407 cites W2003892035 @default.
- W2897502407 cites W2008838733 @default.
- W2897502407 cites W2013292266 @default.
- W2897502407 cites W2017988098 @default.
- W2897502407 cites W2020258717 @default.
- W2897502407 cites W2029478951 @default.
- W2897502407 cites W2034717109 @default.
- W2897502407 cites W2035879375 @default.
- W2897502407 cites W2036893053 @default.
- W2897502407 cites W2037749979 @default.
- W2897502407 cites W2039926575 @default.
- W2897502407 cites W2040585289 @default.
- W2897502407 cites W2056362028 @default.
- W2897502407 cites W2064512432 @default.
- W2897502407 cites W2065266996 @default.
- W2897502407 cites W2071342874 @default.
- W2897502407 cites W2072020283 @default.
- W2897502407 cites W2073607142 @default.
- W2897502407 cites W2074389578 @default.
- W2897502407 cites W2078594804 @default.
- W2897502407 cites W2080092207 @default.
- W2897502407 cites W2085225648 @default.
- W2897502407 cites W2089492568 @default.
- W2897502407 cites W2092790181 @default.
- W2897502407 cites W2096843723 @default.
- W2897502407 cites W2098333708 @default.
- W2897502407 cites W2101520378 @default.
- W2897502407 cites W2112612062 @default.
- W2897502407 cites W2117701544 @default.
- W2897502407 cites W2118599135 @default.
- W2897502407 cites W2122838899 @default.
- W2897502407 cites W2123532192 @default.
- W2897502407 cites W2125775418 @default.
- W2897502407 cites W2129559551 @default.
- W2897502407 cites W2134510352 @default.
- W2897502407 cites W2135453228 @default.
- W2897502407 cites W2136378686 @default.
- W2897502407 cites W2137509535 @default.
- W2897502407 cites W2138226936 @default.
- W2897502407 cites W2139381664 @default.
- W2897502407 cites W2142947451 @default.
- W2897502407 cites W2151757382 @default.
- W2897502407 cites W2156115290 @default.
- W2897502407 cites W2167277304 @default.
- W2897502407 cites W2214184689 @default.
- W2897502407 cites W2219086625 @default.
- W2897502407 cites W2287940103 @default.
- W2897502407 cites W2295700944 @default.
- W2897502407 cites W2342560946 @default.
- W2897502407 cites W2484529140 @default.
- W2897502407 cites W2547914932 @default.
- W2897502407 cites W2571017480 @default.
- W2897502407 cites W2602699833 @default.
- W2897502407 cites W2609731092 @default.
- W2897502407 cites W2754574717 @default.
- W2897502407 cites W2772513561 @default.
- W2897502407 cites W4211182003 @default.
- W2897502407 cites W4242147048 @default.
- W2897502407 doi "https://doi.org/10.1152/ajplung.00196.2018" @default.
- W2897502407 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6337008" @default.
- W2897502407 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30335499" @default.
- W2897502407 hasPublicationYear "2018" @default.
- W2897502407 type Work @default.
- W2897502407 sameAs 2897502407 @default.
- W2897502407 citedByCount "23" @default.
- W2897502407 countsByYear W28975024072019 @default.
- W2897502407 countsByYear W28975024072020 @default.