Sci. STKE, 6 February 2007
Cell Biology Maintaining a Barrier
Elizabeth M. Adler
Science's STKE, AAAS, Washington, DC 20005, USA
Airway epithelial cells require effective mechanisms to repair damage after injuries and maintain a barrier against airborne pathogens and toxins. Wesley et al. used confluent monolayers of normal human bronchial epithelial (NHBE) cells or immortalized human tracheobronchial epithelial cells (HBE1) to investigate mechanisms of airway epithelial repair. Wounded monolayers released adenosine triphosphate (ATP) into the medium, and 1 to 10 µM exogenous ATP enhanced wound closure and promoted HBE1 cell migration. Pharmacological blockade of P2 purinergic receptors (with suramin or Cibracon blue) or hydrolysis of ATP and adenosine diphosphate (ADP) (with apyrase) inhibited wound closure and migration. ATP stimulated H2O2 production, and fluorescence microscopy of indicator-loaded cells revealed a localized increase in H2O2 near wounds. Wound-induced H2O2 production was inhibited by suramin and apyrase; further, basal, ATP-stimulated, and wound-induced H2O2 production were all inhibited in HBE1 cells by siRNA directed against dual oxidase 1 (Duox1, an NADPH oxidase homolog expressed in tracheobronchial epithelial cells). Expression in HBE1 cells of siRNA directed against Duox1 inhibited wound closure and cell migration; a pharmacological inhibitor of NADPH oxidase had effects similar to those of Duox1 knockdown and was also effective in NHBE cells. Wounding also stimulated extracellular signal-regulated kinase (ERK) activation, matrix metalloproteinase-9 expression, and gelatinase activity, all of which were inhibited by suramin and Duox1 knockdown. Thus, the authors conclude that Duox1 is activated by an ATP-dependent mechanism to play a key role in the repair of airway epithelium.
U. V. Wesley, P. F. Bove, M. Hristova, S. McCarthy, A. van der Vliet, Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1. J. Biol. Chem. 282, 3213-3220 (2007). [Abstract] [Full Text]
Citation: E. M. Adler, Maintaining a Barrier. Sci. STKE 2007, tw45 (2007).
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