BACKGROUND: House dust mites (HDMs) are the most important source of indoor aeroallergens that contribute to the rising incidence of @entity56 such as @entity56 . The major HDM, Der f 2, induces inflammatory cytokine expression. Little is known about the signaling pathway involved. OBJECTIVE: We wanted to define the Der f 2 signaling pathway from its receptor to the transcription factor responsible for @entity1312 expression and production. METHODS: @entity1 bronchial epithelial cells were stimulated with Der f 2. The release and gene expression of @entity1312 were measured by means of ELISA and RT-PCR, respectively. In the airway inflammation @entity19 model, airway responses were assessed using ELISA, histology, BAL fluid, and @entity2710 responsiveness. RESULTS: Here, we show that Der f 2 binds to @entity1990 and induces @entity1312 expression and production. In the airway inflammation @entity19 model, Der f 2-induced @entity1312 production significantly decreased with treatment of @entity34041 , a novel @entity1990 inhibitor. Activation of @entity1990 by Der f 2 requires the recruitment and activation of @entity26511 , which leads to phosphorylation of PLCy and membrane translocation of @entity18335 . @entity1995 is then activated by @entity18335 and stimulates @entity60992 activity by phosphorylating the Thr147 residue of @entity60992 . @entity60992 activation enhanced binding of @entity8235 to @entity37362 and leads to increased expression of @entity1312 . CONCLUSION: Our data extend the knowledge for a variety of possible roles of @entity60992 in @entity56 including @entity565 pathogenesis and suggest possible candidacy of @entity60992 as a molecular target for novel therapeutic approaches.

The @entity1990 -associated phospholipase D1 activation is crucial for Der f 2-induced XXXX production.

@entity1 :: ('9606', 'Species') :: ['Human'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity60992 :: ('18805(Tax:10090)', 'Gene') :: ['PLD1'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity8235 :: ('19877(Tax:10090)', 'Gene') :: ['ROCK1'] @entity18335 :: ('18750(Tax:10090)', 'Gene') :: ['PKCa'] @entity56 :: ('MESH:D004342', 'Disease') :: ['allergic disorders', 'allergic diseases', 'allergic asthma'] @entity26511 :: ('20963(Tax:10090)', 'Gene') :: ['Syk'] @entity1312 :: ('16163(Tax:10090)', 'Gene') :: ['IL-13'] @entity37362 :: ('11909(Tax:10090)', 'Gene') :: ['ATF-2'] @entity1990 :: ('21898(Tax:10090)', 'Gene') :: ['TLR4'] @entity34041 :: ('MESH:C507035', 'Chemical') :: ['TAK-242'] @entity2710 :: ('MESH:D016210', 'Chemical') :: ['methacholine'] @entity1995 :: ('26416(Tax:10090)', 'Gene') :: ['p38 MAPK']
@entity1312 :: (16163(Tax:10090),Gene) :: ['IL-13']
