IL-1 upregulates keratinocyte growth factor and hepatocyte growth factor mRNA and protein production by cultured stromal fibroblast cells: interleukin-1 beta expression in the cornea.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Weng
J
J
Eye Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
Mohan
R R
RR
Li
Q
Q
Wilson
S E
SE
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured; D003315:Cornea / Q000378:metabolism; D003319:Corneal Stroma / Q000166:cytology / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis*; D011817:Rabbits; D015854:Up-Regulation
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D007375:Interleukin-1; C034477:RNA primers; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D012313:RNA; D017228:Hepatocyte Growth Factor