Published ahead of print on July 15, 2004, doi:10.1165/rcmb.2003-0433OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0433OC Epidermal Growth Factor and Trefoil Factor Family 2 Synergistically Trigger Chemotaxis on BEAS-2B Cells via Different Signaling CascadesInstitut für Molekularbiologie und Medizinische Chemie, Otto-von-Guericke-Universität, Magdeburg, Germany; and Department of Protein Chemistry, Novo Nordisk A/S, Bagsvaerd, Denmark Address correspondence to: Prof. Werner Hoffmann, Institut für Molekularbiologie und Medizinische Chemie, Universitätsklinikum, Leipziger Str. 44, D-39120 Magdeburg, Germany. E-mail: Werner.Hoffmann{at}Medizin.Uni-Magdeburg.de
Injured areas of the respiratory epithelium are subject to rapid repair by the migration of adjacent epithelial cells, a process termed "restitution". Rapid re-epithelialization is promoted by interactions between migrating cells and the extracellular matrix proteins. Furthermore, epidermal growth factor (EGF) as well as trefoil factor family (TFF) peptides are well known regulators of epithelial restitution due to their motogenic effects. Migration of the human bronchial epithelial cell line BEAS-2B in modified Boyden chambers was used as a model system for airway restitution. EGF or recombinant human TFF2 or TFF3 showed mainly chemotactic activity. The motogenic response was strictly dependent upon a haptotactic substrate, but to different degrees. EGF induced phosphorylation of extracellular signal–regulated kinases (ERK) 1/2, c-Jun-N-terminal kinase, p38, Akt, and p70S6K in BEAS-2B cells. Using specific inhibitors, the signaling cascades responsible for the motogenic response were shown to differ drastically when EGF was compared with TFF2. The motogenic effect of TFF2 was previously demonstrated to depend on ERK1/2 and protein kinase C activation; whereas the EGF-triggered motogenic response was completely independent of ERK1/2 activation but sensitive to the inhibition of phosphoinositide 3-kinase, p38, protein kinase C, or nuclear factor
Abbreviations: bisindolylmaleimide I hydrochloride, BIS • Dulbecco's modified Eagles medium, DMEM • extracellular matrix, ECM • ethylenediamine-N,N,N',N'-tetraacetic acid, EDTA • ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid, EGTA • epidermal growth factor, EGF • extracellular signal–regulated kinase, ERK • inhibitory protein This article has been cited by other articles:
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B. However, the motogenic effects of EGF and TFF2 are additive. These data suggest that luminal EGF and TFF peptides can act synergistically in the human respiratory epithelium to enhance rapid repair processes in the course of diseases such as asthma. 
