IL-1 Upregulates Keratinocyte Growth Factor and Hepatocyte Growth Factor mRNA and Protein Production by Cultured Stromal Fibroblast Cells

Abstract

To determine whether interleukin 1 beta (IL-1 beta) messenger RNA (mRNA) and protein were expressed in corneal cells and to examine the effects of IL-1 alpha and IL-1 beta on the expression of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) mRNAs and proteins in corneal stromal fibroblasts. IL-1 beta mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-1 beta 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-1 alpha and IL-1 beta were monitored by Northern and Western blotting, respectively. IL-1 beta mRNA is expressed in human primary cultured corneal epithelial, stromal fibroblast, and endothelial cells. IL-1 beta protein was detected in epithelium and endothelium in fresh frozen human and rabbit corneal tissue. Little, if any, IL-1 beta was detected in the unwounded corneal stroma. IL-1 alpha and IL-1 beta at 10 ng/ml upregulated the levels of HGF and KGF mRNAs and proteins in cultured human corneal fibroblasts. IL-1 alpha and IL-1 beta 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-1 alpha and IL-1 beta 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.