Breuhahn K, Mann A, Müller G, Wilhelmi A, Schirmacher P, Enk A, Blessing M
SFB-432, I. Medical Department, Johannes Gutenberg University, Mainz, Germany.
Cell Growth Differ. 2000 Feb;11(2):111-21.
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.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）仅在病理条件下，例如在局部应用肿瘤启动子后、在特应性皮炎（AD）中以及受伤后，才由角质形成细胞大量释放。为了研究这种细胞因子释放的生物学功能，我们构建了在表皮中组成性过表达GM-CSF的转基因小鼠。与非转基因对照相比，转基因小鼠中的肥大细胞和朗格汉斯细胞（LCs）数量增加，但未出现严重炎症。这与该细胞因子在LCs的发育和成熟中的核心作用一致。转基因小鼠表皮中的有丝分裂活性升高，但表皮厚度和分化正常。通过增加表皮中的细胞凋亡来维持体内平衡。我们描述了细胞凋亡调节因子的差异表达，并讨论了GM-CSF对角质形成细胞这种新型促凋亡活性的潜在机制。增殖刺激和凋亡促进都与肿瘤发生密切相关。后者可能是在遗传毒性应激或损伤后清除受损细胞的一种方式。
