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

Kuderer NM, San-Juan-Vergara HG, Kong X, Esch R, Lockey RF, Mohapatra SS - Clin Mol Allergy (2003)

Bottom Line: RESULTS: Each of these antigens induced a significant increase in IL-8 levels compared to the medium control.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joy McCann Culverhouse Airway Disease Center, University of South Florida and James A Haley VA Hospital, Tampa, FL, USA. smohapat@hsc.usf.edu

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.

No MeSH data available.


Related in: MedlinePlus

Analysis of Promoters of il6, il8, and rantes. All of these promoters have DNA elements recognized by transcription factors such as AP-1 and NFκB, whose activation is dependent primarily on the ERK activation.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC312598&req=5

Figure 1: Analysis of Promoters of il6, il8, and rantes. All of these promoters have DNA elements recognized by transcription factors such as AP-1 and NFκB, whose activation is dependent primarily on the ERK activation.

Mentions: Previous studies have demonstrated the allergen-induced expression of IL-6, IL-8, ICAM-1 and RANTES [9-11] in epithelial cells. Analysis of the promoter regions of these genes has revealed several cis-regulatory elements (Fig 1). Thus, IL-6 gene contains 3 AP1 and 1 NFκB sites [18,19] and IL-8 gene has 2 AP1 and 1 NFκB sites [20]. Similarly, murine RANTES gene contains 2 AP1 and 2NFκB sites [21,22]. MAPKs are involved in AP1 activation, which in turn, activates NFκB [23]. Furthermore, serine proteases bind to PAR-2 and activate MAPKs [24]. On the basis of these observations, we postulated that A549 cells produce cytokines in response to antigen exposure by activating MAPKs.


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

Kuderer NM, San-Juan-Vergara HG, Kong X, Esch R, Lockey RF, Mohapatra SS - Clin Mol Allergy (2003)

Analysis of Promoters of il6, il8, and rantes. All of these promoters have DNA elements recognized by transcription factors such as AP-1 and NFκB, whose activation is dependent primarily on the ERK activation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC312598&req=5

Figure 1: Analysis of Promoters of il6, il8, and rantes. All of these promoters have DNA elements recognized by transcription factors such as AP-1 and NFκB, whose activation is dependent primarily on the ERK activation.
Mentions: Previous studies have demonstrated the allergen-induced expression of IL-6, IL-8, ICAM-1 and RANTES [9-11] in epithelial cells. Analysis of the promoter regions of these genes has revealed several cis-regulatory elements (Fig 1). Thus, IL-6 gene contains 3 AP1 and 1 NFκB sites [18,19] and IL-8 gene has 2 AP1 and 1 NFκB sites [20]. Similarly, murine RANTES gene contains 2 AP1 and 2NFκB sites [21,22]. MAPKs are involved in AP1 activation, which in turn, activates NFκB [23]. Furthermore, serine proteases bind to PAR-2 and activate MAPKs [24]. On the basis of these observations, we postulated that A549 cells produce cytokines in response to antigen exposure by activating MAPKs.

Bottom Line: RESULTS: Each of these antigens induced a significant increase in IL-8 levels compared to the medium control.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joy McCann Culverhouse Airway Disease Center, University of South Florida and James A Haley VA Hospital, Tampa, FL, USA. smohapat@hsc.usf.edu

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.

No MeSH data available.


Related in: MedlinePlus