Protein kinase C and ERK activation are required for TFF-peptide-stimulated bronchial epithelial cell migration and tumor necrosis factor-α-induced interleukin-6 (IL-6) and IL-8 secretion

被引:83
作者
Graness, A
Chwieralski, CE
Reinhold, D
Thim, L
Hoffmann, W
机构
[1] Otto von Guericke Univ, Inst Mol Biol & Med Chem, D-39120 Magdeburg, Germany
[2] Otto von Guericke Univ, Inst Immunol, D-39120 Magdeburg, Germany
[3] Novo Nordisk AS, Dept Prot Chem, DK-2880 Bagsvaerd, Denmark
关键词
D O I
10.1074/jbc.M200468200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha-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 (JN-K). A complex differential regulation of tumor necrosis factor-a-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.
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页码:18440 / 18446
页数:7
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