Back to Search
Start Over
Endothelin-1 induces proliferation of human lung fibroblasts and IL-11 secretion through an ET(A) receptor-dependent activation of MAP kinases
- Source :
- Journal of cellular biochemistry. 96(4)
- Publication Year :
- 2005
-
Abstract
- Endothelin-1 (ET-1) is implicated in the fibrotic responses characterizing interstitial lung diseases, as well as in the airway remodeling process occurring in asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal human lung fibroblasts (NHLFs), the ET-1 receptor subtypes, and the intracellular signal transduction pathways involved in the proliferative effects of this peptide. Therefore, cells were exposed to ET-1 in the presence or absence of an overnight pre-treatment with either ETA or ETB selective receptor antagonists. After cell lysis, immunoblotting was performed using monoclonal antibodies against the phosphorylated, active forms of mitogen-activated protein kinases (MAPK). ET-1 induced a significant increase in MAPK phosphorylation pattern, and also stimulated fibroblast proliferation and IL-6/IL-11 release into cell culture supernatants. All these effects were inhibited by the selective ETA antagonist BQ-123, but not by the specific ETB antagonist BQ-788. The stimulatory influence of ET-1 on IL-11, but not on IL-6 secretion, was prevented by MAPK inhibitors. Therefore, such results suggest that in human lung fibroblasts ET-1 exerts a profibrogenic action via an ETA receptor-dependent, MAPK-mediated induction of IL-11 release and cell proliferation. © 2005 Wiley-Liss, Inc.
- Subjects :
- MAPK/ERK pathway
Time Factors
Cell Survival
Endothelin A Receptor Antagonists
Biology
Mitogen-Activated Protein Kinase
Biochemistry
Endothelin B Receptor Antagonist
Humans
Secretion
RNA, Messenger
Phosphorylation
Receptor
Molecular Biology
Lung
Cell Proliferation
IL-6
Endothelin-1
Kinase
Cell growth
Interleukin-6
lung fibroblasts
Cell Biology
ET-1 receptors
Fibroblasts
Interleukin-11
Receptor, Endothelin A
Endothelin 1
MAPK
Receptor, Endothelin B
ET-1
Cell biology
Endothelin B Receptor Antagonists
Intracellular signal transduction
IL-11
Cell culture
Fibroblast
Mitogen-Activated Protein Kinases
Endothelin A Receptor Antagonist
Human
Subjects
Details
- ISSN :
- 07302312
- Volume :
- 96
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of cellular biochemistry
- Accession number :
- edsair.doi.dedup.....df3f10bb9df5060883cf695b8a747259