Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function

Abstract: CFTR is a cAMP-regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl- concentration, which in turn produces an increased interleukin-1β (IL-1β) secretion. The secreted IL-1β then induces an autocrine positive fee...

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Autores principales: Massip Copiz, María Macarena, Clauzure, Mariángeles, Valdivieso, Ángel Gabriel, Santa Coloma, Tomás Antonio
Formato: Artículo
Lenguaje:Inglés
Publicado: Wiley 2019
Materias:
PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8915
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8915
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
spellingShingle PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
topic_facet PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
description Abstract: CFTR is a cAMP-regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl- concentration, which in turn produces an increased interleukin-1β (IL-1β) secretion. The secreted IL-1β then induces an autocrine positive feedback loop, further stimulating IL-1β priming and secretion. Since IL-1β can transactivate the epidermal growth factor receptor (EGFR), we study here the levels of expression for different EGFR ligands in Caco-2/pRS26 cells (expressing shRNA against CFTR resulting in a reduced CFTR expression and activity). The epiregulin (EREG), amphiregulin (AREG), and heparin binding EGF like growth factor (HBEGF) mRNAs, were found overexpressed in Caco-2/pRS26 cells. The EREG mRNA had the highest differential expression and was further characterized. In agreement with its mRNA levels, Western blots (WB) showed increased EREG levels in CFTR-impaired cells. In addition, EREG mRNA and protein levels were stimulated by incubation with exogenous IL-1β and inhibited by the Interleukin 1 receptor type I (IL1R1) antagonist IL1RN, suggesting that the overexpression of EREG is a consequence of the autocrine IL-1β loop previously described for these cells. In addition, the JNK inhibitor SP600125, and the EGFR inhibitors AG1478 and PD168393, also had an inhibitory effect on EREG expression, suggesting that EGFR, activated in Caco-2/pRS26 cells, is involved in the observed EREG upregulation. In conclusion, in Caco-2 CFTR-shRNA cells, the EGFR ligand EREG is overexpressed due to an active IL-1β autocrine loop that indirectly activates EGFR, constituting new signaling effectors for the CFTR signaling pathway, downstream of CFTR, Cl- , and IL-1β.
format Artículo
author Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author_facet Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author_sort Massip Copiz, María Macarena
title Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_short Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_full Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_fullStr Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_full_unstemmed Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_sort epiregulin (ereg) is upregulated through an il-1β autocrine loop in caco-2 epithelial cells with reduced cftr function
publisher Wiley
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8915
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bdutipo_str Repositorios
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