Research

Mite and cockroach proteases activate p44/p42 MAP kinases in human lung epithelial cells

Nicole M Kuderer^1,2 , Homero G San-Juan-Vergara^1,3 , Xiaoyuan Kong^1,2 , Robert Esch⁴ , Richard F Lockey^1,2 and Shyam S Mohapatra^1,2

¹  Joy McCann Culverhouse Airway Disease Center, University of South Florida and James A Haley VA Hospital, Tampa, FL, USA

²  James A. Haley VA Hospital, Tampa, USA

³  Department of Microbiology and Immunology, University of South Florida, USA

⁴  Greer Laboratories, Lenoir, NC, USA

author email corresponding author email

Clinical and Molecular Allergy 2003, 1:1doi:10.1186/1476-7961-1-1

Published:	30 October 2003

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.