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J. Biol. Chem., Vol. 277, Issue 21, 18440-18446, May 24, 2002
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From the TFF-peptides (formerly P-domain peptides, trefoil
factors) are typical secretory products of many mucous epithelia and
are aberrantly secreted during chronic inflammatory diseases. They are
known to enhance the migration of intestinal, corneal, and bronchial
epithelial cells. Using the human bronchial epithelial cell line
BEAS-2B as a model, it is shown here for the first time that
TFF-peptides are capable of modulating the inflammatory response in vitro by regulating tumor necrosis
factor-
Protein Kinase C and ERK Activation Are Required for TFF-
peptide-stimulated Bronchial Epithelial Cell Migration and Tumor
Necrosis Factor-
-induced Interleukin-6 (IL-6) and IL-8
Secretion*
,,
Institut für Molekularbiologie und
Medizinische Chemie, Otto-von-Guericke-Universität, D-39120
Magdeburg, Germany, § Institut für Immunologie,
Otto-von-Guericke-Universität, D-39120 Magdeburg, Germany,
and ¶ Department of Protein Chemistry, Novo Nordisk A/S,
DK-2880 Bagsvaerd, Denmark
-induced secretion of interleukin (IL)-6 and IL-8. In
contrast, TFF2 itself does not change IL-6 and IL-8 secretion but
triggers sustained activation of the extracellular signal-regulated
kinases (ERK1/2) as well as phosphorylation of c-Jun N-terminal kinase
(JNK). A complex differential regulation of tumor necrosis
factor--induced IL-6 and IL-8 secretion by TFF2 is observed that
involves signaling via protein kinase C and ERK1/2. Furthermore, the
motogenic effect of TFF2 on BEAS-2B cells is analyzed using a modified
Boyden chamber assay. This migratory effect is shown to be dependent
not only on protein kinase C and ERK1/2 but also on the activation of
the Src family of tyrosine kinases. Taken together, the data presented indicate an important physiological role of TFF-peptides during inflammatory conditions of mucous epithelia.
*
This work was supported by Grants 1918A/0025H and
1918A/2587B from the Land Sachsen-Anhalt (to W. H.), Grants 0163615 and 0500058 from the "Fonds der Chemischen Industrie" (to W. H.), and Grant NBL3/01ZZ0107/project PP20 from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (BMBF; to W .H.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Institut
für Molekularbiologie und Medizinische Chemie,
Universitätsklinikum, Leipziger Str. 44, D-39120 Magdeburg,
Germany. Fax: 49-391-67-13-096; E-mail:
Werner.Hoffmann@Medizin.Uni-Magdeburg.de.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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