Document Detail


Interleukin-7 modulates extracellular matrix production and TGF-beta signaling in cultured human subconjunctival fibroblasts.
MedLine Citation:
PMID:  16769608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: We examined the role of interleukin-7 (IL-7) in modulation of production of extracellular matrix (ECM), immunolocalization of Smads, and cell migration and expressions of transforming growth factor-beta (TGF-beta) in cultured human subconjunctival fibroblasts. IL-7 is capable of inducing Smad7, an inhibitory Smad that interferes with TGF-beta/Smad signal. METHODS: The effects of IL-7 on ECM production, immunolocalization of Smads, type I collagen, fibronectin, alpha -smooth muscle actin (alpha -SMA), and cell migration were examined in human subconjunctival fibroblast culture with or without TGF-beta1. ECM production, such as type I collagen and fibronectin, was measured by immunoassay or real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Cell migration was examined using an in vitro wound model in monolayer cultures. We also examined the effects of IL-7, PKC inhibitor, and STAT inhibitor on the expressions of TGF-beta1 and type I collagen alpha1 chain (col1A1) m-RNA by using real-time RT-PCR. RESULTS: IL-7 reduced the ECM production much more markedly in the cells treated with TGF-1beta than in the control fibroblasts. TGF-beta1 strongly showed immunolocalization of phospho-Smad2, and IL-7 also showed immunolocalization of Smad7 in the nuclei. The immunoreactivities of alpha -SMA and fibronectin were weaker in the presence of IL-7 than in the control cells. IL-7 also delayed defect closure in the monolayer cell sheets, and the delay was recovered by exogenous type I collagen or fibronectin. Each of IL-7, BIS I, or AGS 490 reduced the mRNA expressions of TGF-beta1 and col1A1. CONCLUSIONS: These findings indicate that IL-7 is involved in ECM production in the subconjunctival fibroblasts activated by exogenous TGF-beta1, suggesting that administration of IL-7 can be a novel therapeutic strategy in preventing undesirable bleb scar formation during healing after filtration surgery.
Authors:
Osamu Yamanaka; Shizuya Saika; Kazuo Ikeda; Ken-Ichi Miyazaki; Yoshitaka Ohnishi; Akira Ooshima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current eye research     Volume:  31     ISSN:  0271-3683     ISO Abbreviation:  Curr. Eye Res.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-13     Completed Date:  2006-08-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  491-9     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. yamanaka@wakayama-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics
Cell Movement / drug effects
Cells, Cultured
Collagen Type I / genetics
Conjunctiva / cytology,  drug effects*,  metabolism
Extracellular Matrix / metabolism*
Extracellular Matrix Proteins / biosynthesis*
Fibroblasts / drug effects,  metabolism
Fibronectins / genetics
Humans
Interleukin-7 / pharmacology*
RNA, Messenger / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Smad Proteins / metabolism
Transforming Growth Factor beta / genetics,  metabolism*,  pharmacology
Transforming Growth Factor beta1
Wound Healing / drug effects
Chemical
Reg. No./Substance:
0/Actins; 0/Collagen Type I; 0/Extracellular Matrix Proteins; 0/Fibronectins; 0/Interleukin-7; 0/RNA, Messenger; 0/Smad Proteins; 0/TGFB1 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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