• Login
    View Item 
    •   Athenaeum Home
    • BioMed Central Open Access Articles
    • Open Access Articles by UGA Faculty
    • View Item
    •   Athenaeum Home
    • BioMed Central Open Access Articles
    • Open Access Articles by UGA Faculty
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Selective regulation of MAP kinases and Chemokine expression after ligation of ICAM-1 on human airway epithelial cells

    Thumbnail
    View/Open
    1465-9921-7-12.xml (82.88Kb)
    1465-9921-7-12.pdf (764.7Kb)
    Date
    2006-01-23
    Author
    Krunkosky, Thomas M
    Jarrett, Carla L
    Metadata
    Show full item record
    Abstract
    Abstract Background Intercellular adhesion molecule 1 (ICAM-1) is an immunoglobulin-like cell adhesion molecule expressed on the surface of multiple cell types, including airway epithelial cells. It has been documented that cross-linking ICAM-1 on the surface of leukocytes results in changes in cellular function through outside-inside signaling; however, the effect of cross-linking ICAM-1 on the surface of airway epithelial cells is currently unknown. The objective of this study was to investigate whether or not cross-linking ICAM-1 on the surface of airway epithelial cells phosphorylated MAP kinases or stimulated chemokine expression and secretion. Methods The human lung adenocarcinoma (A549) cells and primary cultures of normal human bronchial epithelial (NHBE) cells were used in these studies. To increase ICAM-1 surface expression, cultures were stimulated with TNFα to enhance ICAM-1 surface expression. Following ICAM-1 upregulation, ICAM-1 was ligated with a murine anti-human ICAM-1 antibody and subsequently cross-linked with a secondary antibody (anti-mouse IgG(ab')2) in the presence or absence of the MAP kinase inhibitors. Following treatments, cultures were assessed for MAPK activation and chemokine gene expression and secretion. Control cultures were treated with murine IgG1 antibody or murine IgG1 antibody and anti-mouse IgG(ab')2 to illustrate specificity. Data were analyzed for significance using a one-way analysis of variance (ANOVA) with Bonferroni post-test correction for multiple comparisons, and relative gene expression was analyzed using the 2-ΔΔCT method. Results ICAM-1 cross-linking selectively phosphorylated both ERK and JNK MAP kinases as detected by western blot analysis. In addition, cross-linking resulted in differential regulation of chemokine expression. Specifically, IL-8 mRNA and protein secretion was not altered by ICAM-1 cross-linking, in contrast, RANTES mRNA and protein secretion was induced in both epithelial cultures. These events were specifically inhibited by the ERK inhibitor PD98059. Data indicates that ICAM-1 cross-linking stimulates a synergistic increase in TNFα-mediated RANTES production involving activation of ERK in airway epithelial cells. Conclusion Results demonstrate that cytokine induced ICAM-1 on the surface of airway epithelial cells induce outside-inside signaling through cross-linking ICAM-1, selectively altering intracellular pathways and cytokine production. These results suggest that ICAM-1 cross-linking can contribute to inflammation in the lung via production of the chemokine RANTES.
    URI
    http://dx.doi.org/10.1186/1465-9921-7-12
    http://hdl.handle.net/10724/19797
    Collections
    • Open Access Articles by UGA Faculty

    About Athenaeum | Contact Us | Send Feedback
     

     

    Browse

    All of AthenaeumCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    About Athenaeum | Contact Us | Send Feedback