IL-1 Upregulates Keratinocyte Growth Factor and Hepatocyte Growth Factor mRNA and Protein Production by Cultured Stromal Fibroblast Cells: Interleukin-1β Expression in the Cornea

Purpose. To determine whether interleukin 1β (IL-1β) messenger RNA (mRNA) and protein were expressed in corneal cells and to examine the effects of IL-1α and IL-1β on the expression of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) mRNAs and proteins in corneal stromal fibroblasts. Methods. IL-1β mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-1β protein was detected by immunohistologic tests. Changes in the expression of HGF and KGF mRNAs and proteins in response to stimulation of cultured corneal stromal fibroblasts with IL-la and IL-1β were monitored by Northern and Western blotting, respectively. Results. IL-1β mRNA is expressed in human primary cultured corneal epithelial, stromal fibroblast, and endothelial cells. IL-1β protein was detected in epithelium and endothelium in fresh frozen human and rabbit corneal tissue. Little, if any, IL-1β was detected in the unwounded corneal stroma. IL-1α and IL-1β at 10 ng/ml upregulated the levels of HGF and KGF mRNAs and proteins in cultured human corneal fibroblasts. Conclusions. IL-1α and IL-1β may serve as key modulators in an epithelial-stromal regulatory loop in the cornea. These data and previously published observations support the hypothesis that corneal epithelial wounding releases IL-1α and IL-1β from epithelial cells; these cytokines in turn upregulate HGF and KGF mRNA and protein levels in keratocytes, and HGF and KGF released by the keratocytes modulate healing of the wounded corneal epithelial cells by regulating proliferation, motility, and differentiation