Interleukin-7 modulates extracellular matrix production and TGF-beta signaling in cultured human subconjunctival fibroblasts

Curr Eye Res. 2006 Jun;31(6):491-9. doi: 10.1080/02713680600701380.


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.

MeSH terms

  • Actins / genetics
  • Cell Movement / drug effects
  • Cells, Cultured
  • Collagen Type I / genetics
  • Conjunctiva / cytology
  • Conjunctiva / drug effects*
  • Conjunctiva / metabolism
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / biosynthesis*
  • Fibroblasts / drug effects
  • Fibroblasts / 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
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Wound Healing / drug effects


  • Actins
  • Collagen Type I
  • Extracellular Matrix Proteins
  • Fibronectins
  • Interleukin-7
  • RNA, Messenger
  • Smad Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1