Korean J Otolaryngol-Head Neck Surg.  2002 Apr;45(4):374-379.

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

• Noh HI
• Kang SJ
• Chae SY
• Park YJ
• Cho SH

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.

Keyword

Keratinocyte growth factor; Keratinocyte growth factor receptor; Interleukin-1beta; Oropharyngeal three-dimensional culture system

MeSH Terms

Cell Communication
Cell Proliferation
Coculture Techniques
Collagen
Cytokines
Cytoplasm
Dermis
Epidermis
Epithelial Cells
Epithelium
Extracellular Matrix
Fibroblast Growth Factor 7*
Fibroblast Growth Factors
Fibroblasts*
Gels
Hepatocyte Growth Factor
Homeostasis
Intercellular Signaling Peptides and Proteins
Interleukin-1beta
Keratinocytes*
Mouth Mucosa
Mucous Membrane
Protein-Tyrosine Kinases
Collagen
Cytokines
Fibroblast Growth Factor 7
Fibroblast Growth Factors
Gels
Hepatocyte Growth Factor
Intercellular Signaling Peptides and Proteins
Interleukin-1beta
Protein-Tyrosine Kinases