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Abstract #13733 Published in IGR 8-2
Interleukin-7 modulates extracellular matrix production and tgf-β signaling in cultured human subconjunctival fibroblasts
Yamanaka O; Saika S; Ikeda K; Miyazaki K; Ohnishi Y; Ooshima ACurrent Eye Research 2006; 31: 491-499
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-β (TGF-β) in cultured human subconjunctival fibroblasts. IL-7 is capable of inducing Smad7, an inhibitory Smad that interferes with TGF-β/Smad signal. METHODS: The effects of IL-7 on ECM production, immunolocalization of Smads, type I collagen, fibronectin, α-smooth muscle actin (α-SMA), and cell migration were examined in human subconjunctival fibroblast culture with or without TGF-β1. 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-β1 and type I collagen α1 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-1β than in the control fibroblasts. TGF-β1 strongly showed immunolocalization of phospho-Smad2, and IL-7 also showed immunolocalization of Smad7 in the nuclei. The immunoreactivities of α-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-β1 and col1A1. CONCLUSIONS: These findings indicate that IL-7 is involved in ECM production in the subconjunctival fibroblasts activated by exogenous TGF-β1, suggesting that administration of IL-7 can be a novel therapeutic strategy in preventing undesirable bleb scar formation during healing after filtration surgery.
Dr. O. Yamanaka, Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
Classification:
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
