Transforming Growth Factor-  and Epidermal Growth Factor Activate Mitogen-Activated Protein Kinase and Its Substrates in Intestinal Epithelial Cells

1995 ◽  
Vol 210 (2) ◽  
pp. 162-170 ◽  
Author(s):  
B. L. Oliver ◽  
R. I. Sha'afi ◽  
J.-J. Hajjar
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Intestinal Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Intestinal Epithelial ◽  
Mitogen Activated Protein ◽  
Epidermal Growth

Epidermal growth factor and interleukin-1β synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells

2004 ◽  
Vol 287 (6) ◽  
pp. G1188-G1193 ◽  
Author(s):  
Katsuhiko Kitagawa ◽  
Yoshinori Hamada ◽  
Yasunori Kato ◽  
Koji Nakai ◽  
Mikio Nishizawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Simultaneous Addition ◽  
Epidermal Growth ◽  
Inos Induction

Epidermal growth factor (EGF) is one of the trophic factors for intestinal adaptation after small bowel transplantation (SBT). A recent report indicates that nitric oxide (NO) has cytoprotective effects on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of the inducible NO synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT. Intestinal epithelial cells (IEC)-6 were treated with EGF and/or IL-1β in the presence and absence of phosphatidylinositol 3-kinase (PI3-kinase) and EGF receptor kinase inhibitors (LY-294002 and tyrphostin A25). The induction of NO production and iNOS and its signal molecules, including the inhibitory protein of NF-κB (IκB), NF-κB, and Akt, were analyzed. IL-1β stimulated the degradation of IκB and the activation of NF-κB but had no effect on iNOS induction. EGF, which had no effect on the NF-κB activation and iNOS induction, stimulated the upregulation of type 1 IL-1 receptor (IL-1R1) through PI3-kinase/Akt. Simultaneous addition of EGF and IL-1β stimulated synergistically the induction of iNOS, leading to the increased production of NO. Our results indicate that EGF and IL-1β stimulate two essential signals for iNOS induction in IEC-6 cells: the upregulation of IL-1R1 through PI3-kinase/Akt and the activation of NF-κB through IκB kinase, respectively. Simultaneous addition of EGF and IL-1β can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury.

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