The EGF Receptor and HER2 Participate in TNF-α-Dependent MAPK Activation and IL-8 Secretion in Intestinal Epithelial Cells
Joint Authors
Hollenberg, Morley D.
Buret, Andre G.
Jijon, Humberto B.
Hirota, Christina L.
Beck, Paul L.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-09-05
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
TNF-α activates multiple mitogen-activated protein kinase (MAPK) cascades in intestinal epithelial cells (IECs) leading to the secretion of interleukin 8 (IL-8), a neutrophil chemoattractant and an angiogenic factor with tumor promoting properties.
As the epidermal growth factor receptor (EGFR) is a known transducer of proliferative signals and a potent activator of MAPKs, we hypothesized that the EGFR participates in TNF-dependent MAPK activation and IL-8 secretion by intestinal epithelial cells (IECs).
We show that the EGFR is tyrosine-phosphorylated following treatment of IECs (HT-29 and IEC-6) with TNF-α.
This requires EGFR autophosphorylation as it was blocked by the EGFR kinase inhibitor AG1478.
Autophosphorylation was also inhibited by both a Src-kinase inhibitor and the metalloproteinase inhibitor batimastat.
TNF treatment of IECs resulted in the accumulation of soluble TGF-α; treatment of IECs with batimastat suppressed TGF-α release and immunoneutralization of TGF-α resulted in decreased EGFR and ERK phosphorylations.
TNF-α treatment of IECs resulted in an association between EGFR and HER2 and inhibition of HER2 using a specific inhibitor AG879 in combination with AG1478-suppressed TNF-α-dependent ERK phosphorylation and IL-8 release.
Downregulation of HER2 via siRNA resulted in a significant decrease in ERK phosphorylation and a 50% reduction in IL-8 secretion.
American Psychological Association (APA)
Jijon, Humberto B.& Buret, Andre G.& Hirota, Christina L.& Hollenberg, Morley D.& Beck, Paul L.. 2012. The EGF Receptor and HER2 Participate in TNF-α-Dependent MAPK Activation and IL-8 Secretion in Intestinal Epithelial Cells. Mediators of Inflammation،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-1029379
Modern Language Association (MLA)
Jijon, Humberto B.…[et al.]. The EGF Receptor and HER2 Participate in TNF-α-Dependent MAPK Activation and IL-8 Secretion in Intestinal Epithelial Cells. Mediators of Inflammation No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-1029379
American Medical Association (AMA)
Jijon, Humberto B.& Buret, Andre G.& Hirota, Christina L.& Hollenberg, Morley D.& Beck, Paul L.. The EGF Receptor and HER2 Participate in TNF-α-Dependent MAPK Activation and IL-8 Secretion in Intestinal Epithelial Cells. Mediators of Inflammation. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-1029379
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1029379