title: Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls the proliferation and differentiation of mouse epidermal melanocytes from pigmented spots induced by ultraviolet radiation B.
abstract: Repeated exposure of ultraviolet radiation B (UVB) on the dorsal skin of hairless mice induces the development of pigmented spots long after its cessation. The proliferation and differentiation of epidermal melanocytes in UVB-induced pigmented spots are greatly increased, and those effects are regulated by keratinocytes rather than by melanocytes. However, it remains to be resolved what factor(s) derived from keratinocytes are involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, primary melanoblasts (c. 80%) and melanocytes (c. 20%) derived from epidermal cell suspensions of mouse skin were cultured in a basic fibroblast growth factor-free medium supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF induced the proliferation and differentiation of melanocytes in those keratinocyte-depleted cultures. Moreover, an antibody to GM-CSF inhibited the proliferation of melanoblasts and melanocytes from epidermal cell suspensions derived from the pigmented spots of UV-irradiated mice, but not from control mice. Further, the GM-CSF antibody inhibited the proliferation and differentiation of melanocytes co-cultured with keratinocytes derived from UV-irradiated mice, but not from control mice. The quantity of GM-CSF secreted from keratinocytes derived from the pigmented spots of UV-irradiated mice was much greater than that secreted from keratinocytes derived from control mice. Moreover, immunohistochemistry revealed the expression of GM-CSF in keratinocytes derived from the pigmented spots of skin in UV-irradiated mice, but not from normal skin in control mice. These results suggest that GM-CSF is one of the keratinocyte-derived factors involved in regulating the proliferation and differentiation of mouse epidermal melanocytes from UVB-induced pigmented spots.
authors.affiliation: Radiation Hazards Research Group, National Institute of Radiological Sciences, Chiba, Japan. thirobe@nirs.go.jp
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hirobe
authors.forename: Rikako
authors.initials: R
authors.lastname: Furuya
authors.forename: Eijiro
authors.initials: E
authors.lastname: Hara
authors.forename: Izumi
authors.initials: I
authors.lastname: Horii
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsunenaga
authors.forename: Ohji
authors.initials: O
authors.lastname: Ifuku
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008812:Mice, Hairless; D012880:Skin Pigmentation / Q000502:physiology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000906:Antibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor