Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Department of Pharmacology, Center for Biomedical Research, University of Granada, Granada, Spain.
Immunobiology. 2010 Nov;215(11):863-73. doi: 10.1016/j.imbio.2010.01.001. Epub 2010 Jan 13.
Survival and proliferation signals are two processes closely interrelated and finely controlled in most cell types, whose deregulation may lead to carcinogenesis. In the last decade, different studies have suggested that both cellular functions are also intimately associated with other cellular activities such as differentiation and cellular activation, especially in immune cells. The aim of this study was to evaluate the effects of the short-chain fatty acid (SCFA) butyrate on the proliferation and activation state of different cell types involved in inflammatory bowel disease. We focused on intestinal epithelial cells, macrophages and T-lymphocytes, using both primary non-transformed cultures and established cell lines. The results showed that low concentrations of butyrate inhibited the proliferation of all the immune cell types tested in this work, whereas it only induced apoptosis in activated T-lymphocytes, non-differentiated epithelial cells and macrophage cell lines, but not in differentiated epithelial cells or primary macrophages. Butyrate apoptosis induction was mediated by caspase-3/7 activation. This SCFA was only able to modify cell activation, measured as expression of inflammatory cytokines, in those cell types in which apoptosis was induced. In conclusion, our results suggest a cell type-specificity of the immune-modulatory effects of butyrate based on the proliferation/activation characteristic physiology of these processes in different cells types.
存活和增殖信号是大多数细胞类型中两个密切相关且精细调控的过程，其失调可能导致癌变。在过去的十年中，不同的研究表明，这两种细胞功能也与其他细胞活动密切相关，如分化和细胞激活，特别是在免疫细胞中。本研究旨在评估短链脂肪酸（SCFA）丁酸盐对参与炎症性肠病的不同细胞类型的增殖和激活状态的影响。我们专注于肠上皮细胞、巨噬细胞和 T 淋巴细胞，使用未转化的原代培养物和已建立的细胞系。结果表明，丁酸盐的低浓度抑制了本工作中测试的所有免疫细胞类型的增殖，而仅在活化的 T 淋巴细胞、未分化的上皮细胞和巨噬细胞系中诱导细胞凋亡，但在分化的上皮细胞或原代巨噬细胞中则不诱导。丁酸盐诱导的细胞凋亡是通过半胱天冬酶-3/7 的激活介导的。这种 SCFA 仅能改变那些诱导细胞凋亡的细胞类型的细胞激活，即作为炎症细胞因子表达来衡量。总之，我们的结果表明，丁酸盐的免疫调节作用具有细胞类型特异性，这是基于不同细胞类型中这些过程的增殖/激活特征生理学。
