Epidermal overexpression of granulocyte-macrophage colony-stimulating factor induces both keratinocyte proliferation and apoptosis

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by ke ratinocytes in sizeable amounts only under pathological conditions, e.g., a fter topical application of a tumor promoter, in atopic dermatitis (AD), an d after wounding. To study the biological function of this cytokine release , we generated transgenic mice that constitutively overexpress GM-CSF in th e epidermis. An increase in-the numbers of mast cells and Langerhans cells (LCs) in transgenics versus nontransgenic controls was observed but no seve re inflammation. This is consistent with a central role of this cytokine in the development and maturation of LCs, Mitotic activity in the epidermis o f 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 apoptos is and discuss a potential mechanism for this novel proapoptotic activity o f GM-CSF on keratinocytes. Both stimulation of proliferation and promotion of apoptosis are of great relevance to tumorigenesis, The latter may be a m eans of removing damaged cells after genotoxic stress or injury.