3 PATTERNS OF CYTOKINE EXPRESSION POTENTIALLY INVOLVED IN EPITHELIAL-FIBROBLAST INTERACTIONS OF HUMAN OCULAR SURFACE

Signals transmitted from mesenchyme to epithelia or vice versa constit ute the basis of reciprocal epithelial-mesenchymal interactions. As a first step toward understanding epithelial-mesenchymal interactions on the ocular surface where the transit amplifying cell-containing corne al epithelium is anatomically separated from the stem cell-containing limbal epithelium, we sought to characterize the expression patterns o f cytokines and their receptors by primary epithelial and early-passag ed fibroblast cultures of human cornea and limbus. Northern hybridizat ion with oligonucleotide and cDNA probes to a total of 25 cytokines an d 12 of their receptors revealed that the positively expressed cytokin es could be divided into the following four patterns. Type I: TGF-alph a, IL-1 beta, and PDGF-B were expressed exclusively by epithelial cell s but their respective receptors EGFR and IL-1R were predominantly and PDGFR-beta was exclusively expressed by fibroblasts. Type II: IGF-I, TGF-beta 1, -beta 2, LIF, and bFGF, and their receptors were expressed by both epithelial cells and fibroblasts. FGFR-1 (flg) and FGFR-2 (be k) were expressed more by fibroblasts and bFGF was expressed more by c orneal than limbal epithelial cells. Type III: keratinocyte growth fac tor (KCF) and hepatocyte growth factor (HGF) were expressed exclusivel y by fibroblasts and their respective receptors, KGFR and c-met, were predominantly expressed by epithelial cells. Combined with RT-PCR, the quantity of KGF and KGFR transcripts was highest in limbal fibroblast s and epithelial cells, respectively. in contrast, the quantity of HGF and HGFR (c-met) transcripts was highest in corneal fibroblasts and e pithelial cells, respectively. Type IV: M-CSF and IL-8 were expressed by fibroblasts and/or epithelial cells but their receptors were not ex pressed by epithelial cells nor fibroblasts, but by immune or inflamma tory cells. In addition to these potential paracrine actions, autocrin e actions mediated by TCF-alpha/EGFR, IL-1 beta/IL1-R, and bFGF/FGFR-1 were more expressed by corneal than limbal epithelial cells. Immunofl uorescence staining on human corneoscleral cryosections confirmed that EGFR and bFGF were not expressed by the limbal basal epithelium, but expressed strongly by the corneal epithelium, a pattern consistent wit h Northern hybridization. These results indicate that ocular surface e pithelial cells and fibroblasts can express a myriad of cytokines, amo ng which the first three patterns constitute the network of potential epithelial-mesenchymal cytokine dialogues. The difference of certain c ytokine expression between corneal and limbal regions suggests that th is network participates in normal epithelial growth and differentiatio n, and plays an important role in wound healing. (C) 1995 Wiley-Liss, Inc.