Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function

Abstract: Patients with cystic fibrosis (CF) have elevated concentration of cytokines in sputum and a general inflammatory condition. In addition, CF cells in culture produce diverse cytokines in excess, including IL-1b. We have previously shown that IL-1b, at low doses (,30 pM), can stimulate the e...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Clauzure, Mariángeles, Valdivieso, Ángel Gabriel, Massip Copiz, María Macarena, Schulman, Gustavo, Teiber, María Luz, Santa Coloma, Tomás Antonio
Formato: Artículo
Lenguaje:Inglés
Publicado: Dominik Hartl, University of Tübingen, Germany 2019
Materias:
MEDICINA
PROTEINAS
CELULAS EPITELIALES
FIBROSIS QUISTICA
CFTR
GENES
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8675
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8675
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 MEDICINA
PROTEINAS
CELULAS EPITELIALES
FIBROSIS QUISTICA
CFTR
GENES
spellingShingle MEDICINA
PROTEINAS
CELULAS EPITELIALES
FIBROSIS QUISTICA
CFTR
GENES
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Massip Copiz, María Macarena
Schulman, Gustavo
Teiber, María Luz
Santa Coloma, Tomás Antonio
Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function
topic_facet MEDICINA
PROTEINAS
CELULAS EPITELIALES
FIBROSIS QUISTICA
CFTR
GENES
description Abstract: Patients with cystic fibrosis (CF) have elevated concentration of cytokines in sputum and a general inflammatory condition. In addition, CF cells in culture produce diverse cytokines in excess, including IL-1b. We have previously shown that IL-1b, at low doses (,30 pM), can stimulate the expression of CFTR in T84 colon carcinoma cells, through NF-kB signaling. However, at higher doses (.2.5 ng/ml, ,150 pM), IL-1b inhibit CFTR mRNA expression. On the other hand, by using differential display, we found two genes with reduced expression in CF cells, corresponding to the mitochondrial proteins CISD1 and MTND4. The last is a key subunit for the activity of mitochondrial Complex I (mCx-I); accordingly, we later found a reduced mCx-I activity in CF cells. Here we found that IB3-1 cells (CF cells), cultured in serum-free media, secrete 32365 pg/ml of IL- 1b in 24 h vs 12763 pg/ml for S9 cells (CFTR-corrected IB3-1 cells). Externally added IL-1b (5 ng/ml) reduces the mCx-I activity and increases the mitochondrial (MitoSOX probe) and cellular (DCFH-DA probe) ROS levels of S9 (CFTR-corrected IB3-1 CF cells) or Caco-2/pRSctrl cells (shRNA control cells) to values comparable to those of IB3-1 or Caco-2/pRS26 cells (shRNA specific for CFTR). Treatments of IB3-1 or Caco-2/pRS26 cells with either IL-1b blocking antibody, IL-1 receptor antagonist, IKK inhibitor III (NF-kB pathway) or SB203580 (p38 MAPK pathway), restored the mCx-I activity. In addition, in IB3-1 or Caco-2/pRS26 cells, IL-1b blocking antibody, IKK inhibitor III or SB203580 reduced the mitochondrial ROS levels by ,50% and the cellular ROS levels near to basal values. The AP-1 inhibitors U0126 (MEK1/2) or SP600125 (JNK1/2/3 inhibitor) had no effects. The results suggest that in these cells IL-1b, through an autocrine effect, acts as a bridge connecting the CFTR with the mCx-I activity and the ROS levels.
format Artículo
author Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Massip Copiz, María Macarena
Schulman, Gustavo
Teiber, María Luz
Santa Coloma, Tomás Antonio
author_facet Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Massip Copiz, María Macarena
Schulman, Gustavo
Teiber, María Luz
Santa Coloma, Tomás Antonio
author_sort Clauzure, Mariángeles
title Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function
title_short Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function
title_full Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function
title_fullStr Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function
title_full_unstemmed Disruption of interleukin-1 β autocrine signaling rescues complex I activity and improves ROS levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function
title_sort disruption of interleukin-1 β autocrine signaling rescues complex i activity and improves ros levels in immortalized epithelial cells with impaired cystic fibrosis transmembrane conductance regulator (cftr) function
publisher Dominik Hartl, University of Tübingen, Germany
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8675
work_keys_str_mv AT clauzuremariangeles disruptionofinterleukin1bautocrinesignalingrescuescomplexiactivityandimprovesroslevelsinimmortalizedepithelialcellswithimpairedcysticfibrosistransmembraneconductanceregulatorcftrfunction
AT valdiviesoangelgabriel disruptionofinterleukin1bautocrinesignalingrescuescomplexiactivityandimprovesroslevelsinimmortalizedepithelialcellswithimpairedcysticfibrosistransmembraneconductanceregulatorcftrfunction
AT massipcopizmariamacarena disruptionofinterleukin1bautocrinesignalingrescuescomplexiactivityandimprovesroslevelsinimmortalizedepithelialcellswithimpairedcysticfibrosistransmembraneconductanceregulatorcftrfunction
AT schulmangustavo disruptionofinterleukin1bautocrinesignalingrescuescomplexiactivityandimprovesroslevelsinimmortalizedepithelialcellswithimpairedcysticfibrosistransmembraneconductanceregulatorcftrfunction
AT teibermarialuz disruptionofinterleukin1bautocrinesignalingrescuescomplexiactivityandimprovesroslevelsinimmortalizedepithelialcellswithimpairedcysticfibrosistransmembraneconductanceregulatorcftrfunction
AT santacolomatomasantonio disruptionofinterleukin1bautocrinesignalingrescuescomplexiactivityandimprovesroslevelsinimmortalizedepithelialcellswithimpairedcysticfibrosistransmembraneconductanceregulatorcftrfunction
bdutipo_str Repositorios
_version_ 1764820528415113216

Ejemplares similares