Turksen K, Kupper T, Degenstein L, Williams I, Fuchs E
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5068-72. doi: 10.1073/pnas.89.11.5068.
Interleukin 6 (IL-6) is a cytokine that mediates a wide range of inflammatory and immune responses. Its expression is elevated in inflammatory or immunodeficient diseases, including psoriasis, rheumatoid arthritis, and AIDS. To explore the role of IL-6 in skin, we utilized a human keratin 14 (K14) promoter to express IL-6 in the basal cells of stratified squamous epithelia of transgenic mice. Mice expressing the K14-IL-6 transgene were smaller than normal and exhibited retarded hair growth. Surprisingly, IL-6 expression did not lead to enhanced epidermal proliferation, but it did result in a thicker stratum corneum, with an otherwise seemingly normal program of differentiation. IL-6 expression did not lead to leukocytic infiltration, making it unlikely that it has direct proinflammatory activity in skin. Based on this study, one role of IL-6 relevant to host defense may be to enhance the stratum corneum, thereby providing increased protection from injurious stimuli or infection. If IL-6 plays additional roles in the skin, it is likely to act synergistically with factors that IL-6 alone cannot induce.
白细胞介素6(IL-6)是一种介导多种炎症和免疫反应的细胞因子。其表达在包括银屑病、类风湿性关节炎和艾滋病在内的炎症或免疫缺陷疾病中升高。为了探究IL-6在皮肤中的作用,我们利用人角蛋白14(K14)启动子在转基因小鼠复层鳞状上皮的基底细胞中表达IL-6。表达K14-IL-6转基因的小鼠比正常小鼠体型小,且毛发生长迟缓。令人惊讶的是,IL-6的表达并未导致表皮增殖增强,但确实导致角质层增厚,而分化程序在其他方面看似正常。IL-6的表达并未导致白细胞浸润,这使得其在皮肤中不太可能具有直接的促炎活性。基于这项研究,IL-6与宿主防御相关的一个作用可能是增强角质层,从而提供对有害刺激或感染的更强保护。如果IL-6在皮肤中发挥其他作用,它可能与IL-6单独无法诱导的因子协同发挥作用。