Palmitoylethanolamide regulates development of intestinal radiation injury in a mast cell-dependent manner.
Palmitoylethanolamide regulates development of intestinal radiation injury in a mast cell-dependent manner.
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棕榈酰乙醇酰胺以肥大细胞依赖性方式调节肠道辐射损伤的发展。
DOI：
10.1007/s10620-014-3212-5
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发表时间：
2014-11
影响因子：
3.1
通讯作者：
Hauer-Jensen, Martin
中科院分区：
文献类型：
--
作者：
Wang, Junru;Zheng, Junying;Kulkarni, Ashwini;Wang, Wen;Garg, Sarita;Prather, Paul L.;Hauer-Jensen, Martin
肥大细胞和神经免疫相互作用调节肠道放射性粘膜炎的严重程度，这是腹部恶性肿瘤放射治疗期间的一种剂量限制性毒性。由于内源性大麻素对肠道炎症有调节作用，因此我们研究了拟大麻药棕榈酰乙醇胺(PEA)对肥大能力(+/+)和肥大细胞缺陷(Ws/Ws)大鼠模型的影响。大鼠接受局部分次肠道照射，从照射前1d至照射后2周每日注射赋形剂或PEA。通过鲁米诺生物发光无创评估肠道损伤，并在2周后通过组织学、形态计量学、免疫组织化学分析、基因表达分析和通路分析来评估肠道损伤。与+/+大鼠相比，Ws/Ws大鼠的肠道结构损伤(p=0.01)、粘膜损伤(p=0.02)、中性粒细胞浸润(p=0.0003)和胶原沉积(p=0.004)明显增多。PEA可减轻Ws/Ws大鼠的结构辐射损伤(p=0.02)、肠壁厚度(p=0.03)、胶原沉积(p=0.03)和肠道炎症(p=0.02)，但对+/+大鼠无明显影响。PEA可抑制肥大细胞来源的细胞免疫反应和抗炎IL-6、IL-10信号转导，并激活凝血酶原途径。相反，虽然PEA抑制非肥大细胞来源的免疫反应，但它增加了Ws/Ws大鼠的抗炎IL-10和IL-6信号，并减少了凝血酶原通路的激活。这些数据表明，肥大细胞的缺乏可能通过涉及凝血系统、抗炎细胞因子信号和先天免疫系统的机制来加剧放射性肠病；这些机制是由PEA以肥大细胞依赖的方式调节的。应探索内源性大麻素系统作为减轻肠道放射性损伤的靶点。
Mast cells and neuroimmune interactions regulate the severity of intestinal radiation mucositis, a dose-limiting toxicity during radiation therapy of abdominal malignancies. Because endocannabinoids regulate intestinal inflammation, we investigated the effect of the cannabimimetic, palmitoylethanolamide (PEA), in a mast competent (+/+) and mast cell deficient (Ws/Ws) rat model. Rats underwent localized, fractionated intestinal irradiation and received daily injections with vehicle or PEA from 1 day before until 2 weeks after radiation. Intestinal injury was assessed non-invasively by luminol bioluminescence, and, at 2 weeks, by histology, morphometry, and immunohistochemical analysis, gene expression analysis, and pathway analysis. Compared to +/+ rats, Ws/Ws rats sustained more intestinal structural injury (p=0.01), mucosal damage (p=0.02), neutrophil infiltration (p=0.0003), and collagen deposition (p=0.004). PEA reduced structural radiation injury (p=0.02), intestinal wall thickness (p=0.03), collagen deposition (p=0.03), and intestinal inflammation (p=0.02) in Ws/Ws rats, but not in +/+ rats. PEA inhibited mast cell-derived cellular immune response and anti-inflammatory IL-6 and IL-10 signaling, and activated the prothrombin pathway in +/+ rats. In contrast, while PEA suppressed non-mast cell derived immune responses, it increased anti-inflammatory IL-10 and IL-6 signaling and decreased activation of the prothrombin pathway in Ws/Ws rats. These data demonstrate that the absence of mast cells exacerbate radiation enteropathy by mechanisms that likely involve the coagulation system, anti-inflammatory cytokine signaling, and the innate immune system; and that these mechanisms are regulated by PEA in a mast cell-dependent manner. The endocannabinoid system should be explored as target for mitigating intestinal radiation injury.
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影响因子：
--
作者：
Caughey, George H.
通讯作者：
Caughey, George H.
影响因子：
29.4
作者：
GRAHAM, MF;BRYSON, GR;DIEGELMANN, RF
通讯作者：
DIEGELMANN, RF
DOI：
10.1124/jpet.108.136903
发表时间：
2008-07-01
影响因子：
3.5
作者：
Genovese, Tiziana;Esposito, Emanuela;Cuzzocrea, Salvatore
通讯作者：
Cuzzocrea, Salvatore
DOI：
10.1016/0360-3016(88)90399-9
发表时间：
1988-06-01
影响因子：
7
作者：
HAUERJENSEN, M;POULAKOS, L;OSBORNE, JW
通讯作者：
OSBORNE, JW
影响因子：
7.3
作者：
Ho, W-S V.;Barrett, D. A.;Randall, M. D.
通讯作者：
Randall, M. D.