Document Detail

Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts.
MedLine Citation:
PMID:  15857893     Owner:  NLM     Status:  MEDLINE    
Cell-cell signaling roles for reactive oxygen species (ROS) generated in response to growth factors/cytokines in nonphagocytic cells are not well defined. In this study, we show that fibroblasts isolated from lungs of patients with idiopathic pulmonary fibrosis (IPF) generate extracellular hydrogen peroxide (H2O2) in response to the multifunctional cytokine, transforming growth factor-beta1 (TGF-beta1). In contrast, TGF-beta1 stimulation of small airway epithelial cells (SAECs) does not result in detectable levels of extracellular H2O2. IPF fibroblasts independently stimulated with TGF-beta1 induce loss of viability and death of overlying SAECs when cocultured in a compartmentalized Transwell system. These effects on SAECs are inhibited by the addition of catalase to the coculture system or by the selective enzymatic blockade of H2O2 production by IPF fibroblasts. IPF fibroblasts heterogeneously express alpha-smooth muscle actin stress fibers, a marker of myofibroblast differentiation. Cellular localization of H2O2 by a fluorescent-labeling strategy demonstrated that extracellular secretion of H2O2 is specific to the myofibroblast phenotype. Thus, myofibroblast secretion of H2O2 functions as a diffusible death signal for lung epithelial cells. This novel mechanism for intercellular ROS signaling may be important in physiological/pathophysiological processes characterized by regenerating epithelial cells and activated myofibroblasts.
Meghna Waghray; Zongbin Cui; Jeffrey C Horowitz; Indhu M Subramanian; Fernando J Martinez; Galen B Toews; Victor J Thannickal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-02-16
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  19     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-28     Completed Date:  2005-12-22     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  854-6     Citation Subset:  IM    
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
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MeSH Terms
Catalase / pharmacology
Cell Death / drug effects,  physiology*
Cell Division
Cells, Cultured
Coculture Techniques
Epithelial Cells / physiology*
Fibroblasts / physiology*
Fluorescent Antibody Technique
Hydrogen Peroxide / metabolism,  pharmacology*
Muscle Cells / physiology
Oxidative Stress
Pulmonary Fibrosis / metabolism,  pathology*
Signal Transduction*
Transforming Growth Factor beta / pharmacology
Transforming Growth Factor beta1
Grant Support
Reg. No./Substance:
0/TGFB1 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 7722-84-1/Hydrogen Peroxide; EC

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