Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis
Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis
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DOI：
10.1371/journal.pone.0028159
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发表时间：
2011-12-06
期刊：
影响因子：
3.7
通讯作者：
Iuvone, Teresa
中科院分区：
文献类型：
--
作者：
De Filippis, Daniele;Esposito, Giuseppe;Iuvone, Teresa
肠胶质细胞（Enteric glial cells， EGC）积极介导肠道急慢性炎症；EGC增殖并释放神经营养因子、生长因子和促炎细胞因子，反过来，它们可能会增强免疫反应，代表了肠道神经系统和免疫系统之间非常重要的联系。大麻二酚（CBD）是一种有趣的化合物，因为它能够控制中枢神经系统的反应性胶质瘤，而没有任何不必要的精神药物作用。因此，我们研究的基本原理是研究CBD对溃疡性结肠炎（UC）患者和lps诱导的肠道炎症小鼠肠道部分的肠道活检的影响。CBD通过大量降低星形胶质细胞信号神经营养因子S100B，显著抵消lps小鼠的反应性肠胶质细胞形成。组织学、生化和免疫组织化学数据表明，S100B的减少与CBD处理后lps处理小鼠肠道肥大细胞和巨噬细胞的显著减少有关。此外，用CBD治疗lps小鼠可降低tnf - α表达和cleaved caspase-3的存在。在体外培养的人结肠活检中获得了类似的结果。在UC患者的活组织检查中，无论是在活动性炎症期间还是在LPS+ inf - γ刺激下的缓解期，胶质细胞活化增加和肠道损伤都得到了证实。在人体活检中，CBD降低了S100B和iNOS蛋白的表达，证实了其在脓毒症小鼠中的作用。CBD的活性至少部分是通过选择性ppar - γ受体途径介导的。CBD靶向肠反应性胶质瘤，在小鼠和UC患者的人类结肠培养物中抵消LPS诱导的炎症环境。这些作用导致pparγ受体途径介导的肠道损伤减少。因此，我们的研究结果表明，CBD确实揭示了一种治疗炎症性肠病的新治疗策略。
Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-alpha expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-gamma, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.