Document Detail

TLR9 is expressed in idiopathic interstitial pneumonia and its activation promotes in vitro myofibroblast differentiation.
MedLine Citation:
PMID:  18633634     Owner:  NLM     Status:  MEDLINE    
Infectious diseases can be cofactors in idiopathic interstitial pneumonias (IIP) pathogenesis; recent data suggests that toll-like receptors 9 (TLR9) ligands contribute to experimental chronic tissue remodeling. Real-time TAQMAN and immunohistochemical analysis of IIP normal surgical lung biopsies (SLBs), primary fibroblast lines grown from both IIP and normal SLBs indicate that TLR9 is prominently and differentially expressed in a disease-specific manner. TLR9 expression was increased in biopsies from patients with IIP compared with normal lung biopsies and its expression is localized to areas of marked interstitial fibrosis. TLR9 in fibroblasts appeared to be increased by profibrotic Th2 cytokines (IL-4 and IL-13) and this was true in fibroblasts cultured from the most severe form of IIP, idiopathic pulmonary fibrosis (IPF) SLBs, in non-specific interstitial pneumonia fibroblast lines, and in normal fibroblasts. Finally, confocal microscopy studies have shown that TLR9 activation by its synthetic agonist CpG-ODN significantly increased the expression of alpha smooth muscle actin, the main marker of myofibroblast differentiation. These data indicate that TLR9 expression may drive the abnormal tissue healing response in severe forms of IIP and its activation can have a key role in myofibroblast differentiation promoting the progression of disease during the terminal phase of IPF.
A Meneghin; E S Choi; H L Evanoff; S L Kunkel; F J Martinez; K R Flaherty; G B Toews; C M Hogaboam
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-17
Journal Detail:
Title:  Histochemistry and cell biology     Volume:  130     ISSN:  0948-6143     ISO Abbreviation:  Histochem. Cell Biol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-13     Completed Date:  2008-12-11     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  9506663     Medline TA:  Histochem Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  979-92     Citation Subset:  IM    
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MeSH Terms
Actins / metabolism
Cell Differentiation* / drug effects
Cells, Cultured
Fibroblasts / drug effects,  immunology*,  pathology
Idiopathic Interstitial Pneumonias / genetics,  immunology*,  pathology
Idiopathic Pulmonary Fibrosis / genetics,  immunology*,  pathology
Interleukin-13 / metabolism
Interleukin-4 / metabolism
Lung / drug effects,  immunology*,  pathology
Microscopy, Confocal
Oligodeoxyribonucleotides / pharmacology
Polymerase Chain Reaction
RNA, Messenger / metabolism
Recombinant Proteins / metabolism
Toll-Like Receptor 9 / agonists,  genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Actins; 0/CPG-oligonucleotide; 0/Interleukin-13; 0/Oligodeoxyribonucleotides; 0/RNA, Messenger; 0/Recombinant Proteins; 0/TLR9 protein, human; 0/Toll-Like Receptor 9; 207137-56-2/Interleukin-4

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