title: Mite and cockroach proteases activate p44/p42 MAP kinases in human lung epithelial cells.
abstract: BACKGROUND: The mechanisms underlying epithelial cell activation by indoor inhaled antigens are poorly understood. METHODS: In this study, we investigated the role of mitogen-activated protein kinases (MAPKs) in A549 epithelial cells upon exposure to antigens of house dust mite (HDMA), German cockroach (GCA), and American cockroach (ACA). RESULTS: Each of these antigens induced a significant increase in IL-8 levels compared to the medium control. Exposure of A549 cells to these antigens induced the phosphorylation of p44/42 MAPKs within 5 minutes, which reached a peak at 25 minutes later and reached baseline levels at 1 hour after exposure. PD98059, a MEK1 inhibitor, significantly decreased phosphorylation of p44/p42 MAPKs and IL-8 production. Exposure of A549 cells with antigens, which had been preincubated with different protease inhibitors, also resulted in a reduction of both MAPK phosphorylation and IL-8 production. CONCLUSION: Thus, proteolytic antigens present in HDMA, GCA and ACA activate the p44/42 MAPKs airway epithelial cells, which lead to elevated IL-8 production and initiation of the inflammatory cascade.
authors.affiliation: Joy McCann Culverhouse Airway Disease Center, University of South Florida and James A Haley VA Hospital, Tampa, FL, USA. smohapat@hsc.usf.edu
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kuderer
authors.forename: Homero G
authors.initials: HG
authors.lastname: San-Juan-Vergara
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Kong
authors.forename: Robert
authors.initials: R
authors.lastname: Esch
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Mohapatra