Epithelial permeability is distorted by Pseudomonas aeruginosa elastase (PE) and changes in barrier function are caused by disruption of tight junction (TJ) proteins occludin, zonula occludens (ZO)-1 and alterations of the cytoskeleton. Increase in paracellular permeability is caused, in part, by activation of cellular signaling transduction pathways. The exact signaling mechanisms that lead to epithelial disruption are not yet fully understood. I sought to evaluate whether PE exposure can activate the epidermal growth factor receptor (EGFR) and whether, PE-induced TJ disruption was dependent upon activation of the extracellular signal-regulated kinases (ERK) arm of the mitogen-activated protein kinase (MAPK) pathway. My results indicate that inhibition of EGFR attenuated PE induced disruptive changes in expression of TJ proteins occludin and ZO-1. I demonstrate that PE induces phosphorylation of ERK proteins within 5 minutes of apical exposure. Activation of MAPK preceded a loss of localization of TJ proteins occludin and zonula occludens (ZO)-1 and cytoskeletal reorganization. Furthermore, I propose that TJ disruption is elicited, in part, by activation of EGFR/MAPK signaling pathway by Pseudomonas elastase.

Date of publication

Spring 5-17-2013

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