Repair phenotype in corneal fibroblasts is controlled by an interleukin-1 alpha autocrine feedback loop

Invest Ophthalmol Vis Sci. 1997 Jun;38(7):1367-79.


Purpose: To explore the role of autocrine interleukin-1 alpha (IL-1 alpha) as a central regulator of the repair phenotype in corneal fibroblasts.

Methods: Disruption of the actin cytoskeleton with cytochalasin B (CB), which mimics changes in shape that occur in repair tissues, was used to stimulate repair gene expression in early-passage fibroblasts. Changes in expression of IL-1 alpha, IL-8, collagenase, and ENA-78 were determined by Northern blot analysis, radioimmunoassay, and an enzyme-amplified sensitivity immunoassay (EASIA). Expression of repair genes was also examined in repair fibroblasts, isolated from healing, penetrating keratectomy wounds in rabbits.

Results: Blocking IL-1 alpha activity prevented both constitutive and stimulated increases in synthesis of IL-8 and collagenase in early-passage cultures of corneal fibroblasts, demonstrating the role of IL-1 alpha as a necessary intermediate for expression of these genes. Evidence is also presented that the IL-1 alpha autocrine controls expression of an IL-8 related factor, ENA-78. Unlike early-passage fibroblasts, fibroblasts freshly isolated from the uninjured cornea did not express IL-1 alpha. However, fibroblasts freshly isolated from remodeling corneal repair tissue 3 weeks after injury were found to express substantial levels of IL-1 alpha, regulated through an autocrine feedback loop. Neutralization experiments demonstrated that the IL-1 alpha autocrine is largely responsible for controlling both collagenase and IL-8 synthesis in repair fibroblasts, as it is in early-passage fibroblasts.

Conclusions: These findings provide evidence that activation of an autocrine IL-1 alpha feedback loop is an important mechanism by which fibroblasts adopt a repair phenotype during remodeling of the cornea.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Chemokine CXCL5
  • Chemokines, CXC*
  • Collagenases / metabolism
  • Cornea / physiology*
  • Corneal Injuries
  • Eye Injuries, Penetrating / physiopathology
  • Feedback
  • Fibroblasts / physiology*
  • Immunoenzyme Techniques
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Interleukin-8 / analogs & derivatives
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Interleukin-8 / pharmacology
  • Phenotype
  • RNA, Messenger / biosynthesis
  • Rabbits
  • Radioimmunoassay
  • Wound Healing / physiology*


  • CXCL5 protein, human
  • Chemokine CXCL5
  • Chemokines, CXC
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Collagenases