title: Epidermal overexpression of granulocyte-macrophage colony-stimulating factor induces both keratinocyte proliferation and apoptosis.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by keratinocytes in sizeable amounts only under pathological conditions, e.g., after topical application of a tumor promoter, in atopic dermatitis (AD), and after wounding. To study the biological function of this cytokine release, we generated transgenic mice that constitutively overexpress GM-CSF in the epidermis. An increase in the numbers of mast cells and Langerhans cells (LCs) in transgenics versus nontransgenic controls was observed but no severe inflammation. This is consistent with a central role of this cytokine in the development and maturation of LCs. Mitotic activity in the epidemnis of transgenic mice was elevated, but epidermal thickness and differentiation were normal. Homeostasis is maintained by an increase of apoptosis in the epidermis. We describe the differential expression of regulators of apoptosis and discuss a potential mechanism for this novel proapoptotic activity of GM-CSF on keratinocytes. Both stimulation of proliferation and promotion of apoptosis are of great relevance to tumorigenesis. The latter may be a means of removing damaged cells after genotoxic stress or injury.
authors.affiliation: SFB-432, I. Medical Department, Johannes Gutenberg University, Mainz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Breuhahn
authors.forename: A
authors.initials: A
authors.lastname: Mann
authors.forename: G
authors.initials: G
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Wilhelmi
authors.forename: P
authors.initials: P
authors.lastname: Schirmacher
authors.forename: A
authors.initials: A
authors.lastname: Enk
authors.forename: M
authors.initials: M
authors.lastname: Blessing
mesh_terms: D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002455:Cell Division; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology*; D007633:Keratins / Q000096:biosynthesis; D007801:Langerhans Cells / Q000166:cytology; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000502:physiology
chemical_list: D011993:Recombinant Fusion Proteins; D007633:Keratins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor