Tyrosine kinase and MAPK inhibition of TNF-alpha- and EGF-stimulated IEC-6 cell growth

Biochemical and Biophysical Research Communications
S DionneE G Seidman

Abstract

The role of TNF-alpha in modulating intestinal crypt cell growth was examined, in comparison with EGF. Both significantly increased IEC-6 cell proliferation. Neither EGF nor TNF-alpha overcame the inhibitory effect on growth exerted by the tyrosine kinase inhibitor genistein. Immunoblots with phosphotyrosine antibodies showed increased tyrosine phosphorylation of IEC-6 cell proteins in response to EGF and TNF-alpha stimulation. TNF-alpha increased ERK1 and ERK2 MAPK phosphorylation. A MAPK assay confirmed the increased activity upon TNF-alpha stimulation. Selective inhibition of MAPK activation by PD98059 resulted in a dose dependent inhibition of TNF-alpha or EGF-induced IEC-6 cell growth. These findings suggest a role for TNF-alpha in the regulation of intestinal epithelial cell growth and that the mitogenic effect of TNF-alpha requires protein tyrosine phosphorylation and MAPK activation.

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Citations

Oct 27, 2004·The Journal of General Physiology·Ivette AymerichF Javier Casado
Oct 4, 2005·Biochemical and Biophysical Research Communications·S SchwartzF M Ruemmele
Aug 24, 1999·Journal of Cellular Physiology·F M RuemmeleE G Seidman
Oct 18, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sujoy BhattacharyaLeonard R Johnson
Dec 21, 2006·Journal of Cellular Biochemistry·P AmadorM J Rodríguez-Yoldi
Jun 11, 2002·American Journal of Physiology. Cell Physiology·Humberto B JijonHoward G Parsons
Jul 19, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sujoy BhattacharyaLeonard R Johnson
May 9, 2002·American Journal of Physiology. Cell Physiology·Steven S WuEnrique Rozengurt
May 31, 2012·Digestive Diseases and Sciences·Hiromasa NakamizoToshifumi Hibi
Nov 30, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·M S InanC Giardina
Jan 17, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hua YangDaniel H Teitelbaum
Jul 22, 2009·Nutrition·Marie-Josée RoyErnest G Seidman

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