Am. J. Respir. Cell Mol. Biol., Volume 25, Number 4, October, 2001 418-424

Trefoil Factor Family-Peptides Promote Migration of Human Bronchial Epithelial Cells
Synergistic Effect with Epidermal Growth Factor

Martin Oertel, Angela Graness, Lars Thim, Frank Bühling, Hubert Kalbacher, and Werner Hoffmann

Institut für Molekularbiologie und Medizinische Chemie, and Institut für Immunologie, Otto-von-Guericke-Universität, Magdeburg; Medizinisch-Naturwissenschaftliches Forschungszentrum, Eberhard-Karls-Universität, Tübingen, Germany; and Department of Protein Chemistry, Novo Nordisk A/S, Bagsvaerd, Denmark

A process termed "restitution" enables rapid repair of the respiratory epithelium by migration of neighbouring cells. Mucin-associated TFF-peptides (formerly P-domain peptides or trefoil factors) are typical motogens enhancing migration of cells in various in vitro models mimicking restitution of the intestine. The human bronchial epithelial cell line BEAS-2B was used as a model system of airway restitution. The motogenic activities of recombinant human TFF2 as well as porcine TFF2 were demonstrated by in vitro wound healing assays of BEAS-2B cells. TFF2 did not induce phosphorylation of the epidermal growth factor (EGF) receptor. EGF was capable of enhancing the motogenic effect of human TFF2 at a concentration of 3 × 10¹⁰ M whereas EGF itself (i.e., in the absence of TFF2) did not stimulate migration at this low concentration. Furthermore, TFF2 as well as monomeric and dimeric forms of TFF3 enhanced migration of BEAS-2B cells in Boyden chambers. Motogenic activity of TFF2 was also shown for normal human bronchial epithelial (NHBE) cells in Boyden chambers. These results suggest that TFF-peptides act as motogens in the human respiratory epithelium triggering rapid repair of damaged mucosa in the course of airway diseases such as asthma.

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