Immunohistochemical Expression of IL-1beta Induced Keratinocyte Growth Factor and Its Receptor from Oropharyngeal Fibroblast in the Three Dimensional Culture System / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Epidermal-mesenchymal interactions control epidermal growth and differentiation and thus regulate tissue homeostasis in the epidermis. So the function of fibroblasts is, in addition to producing extracellular matrix as a structural framework, to act as a cellular communication bridge between epidermis and dermis by synthesizing various mediators, such as growth factors and cytokines. Although the epithelial-mesenchymal cell interaction is still not known clearly, cytokines like interleukine-1beta from keratinocyte promote Keratinocyte growth factor (KGF) which is a member of the fibroblast growth factor (FGF-7) group. IL-1beta was shown to be an important modulator of KGF expression by fibroblast cells. Like hepatocyte growth factor, KFG is best characterized as paracrine mediators of stromal-epithelial interactions produced by fibroblast cells to regulate the functions of epithelial cells and the KGF receptors (KGFR) which is a transmembrane tyrosine kinase that is a splice variant of the FGFR-2/bek gene. To study the regulation of epidermal cell proliferation and differentiation by fibroblasts via paracrine effects of oropharyngeal mucosa, an in-vitro model system has been developed to mimic epidermal-dermal interactions. Material and Method: A co-culture of fibroblasts and keratinocytes in three-dimensional collagen gels was treated with IL-1beta after carrying out the tissue culture from oropharyngeal mucosa. Immuno-histochemistry for localization of KFG and KFGR was done in these artificial tissue and in the mucosa. RESULTS: KGF and KGFR proteins were strongly expressed in cytoplasm of intermediate and superficial layers of the epithelium of the oropharyngeal mucosa. In four out of the five cases, three-dimensional oral mucosa cultures were successfully reconstructed on fibroblast-populated collagen lattice. KGF expression was found focally in the keratinocyte of epithelial layer and diffusely in fibroblast-populated collagen lattice. KGFR was only expressed focally in Keratinocyte of epithelial layer. CONCLUSION: Epidermal-mesenchymal interactions in oropharyngeal mucosa via IL-1beta, KGF and KGFR were observed in a three-dimesional culture system, showing that this system could be used as a study model of epidermal-mesenchymal interactions in oropharyngeal mucosa with some limitations.