Sodium chloride exacerbates dextran sulfate sodium-induced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice.
Sodium chloride exacerbates dextran sulfate sodium-induced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice.
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氯化钠通过 p38/MAPK 通路调节促炎和抗炎固有层单核细胞，加剧小鼠硫酸葡聚糖钠诱导的结肠炎
DOI：
10.3748/wjg.v24.i16.1779
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发表时间：
2018-04-28
影响因子：
4.3
通讯作者：
Li JT
中科院分区：
文献类型：
--
作者：
Guo HX;Ye N;Yan P;Qiu MY;Zhang J;Shen ZG;He HY;Tian ZQ;Li HL;Li JT
目的研究高盐对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的影响，并探讨其作用机制。方法采用DSS和NaCl建立致炎动物模型。我们评估了结肠炎的严重程度。采用流式细胞术检测脾脏、肠系膜淋巴结和固有层Th 1、巨噬细胞和T细胞亚群的比例。通过用氯膦酸盐脂质体消耗巨噬细胞来评价巨噬细胞在NaCl促进DSS诱导的结肠炎中的重要作用。用NaCl刺激活化的腹腔巨噬细胞和固有层单核细胞（LPMCs），并用Western印迹法检测蛋白质。采用酶联免疫吸附试验和RT-PCR检测细胞因子和炎症相关基因。结果NaCl可上调DSS处理小鼠固有层中CD 11b+巨噬细胞和CD 4 +IFN-γ+IL-17+ T细胞的比例。CD 3 + CD 4 + CD 25 + Foxp 3 + T细胞可分泌高水平的IL-10和TGF-β，在NaCl和DSS处理的小鼠中通过反馈增加。此外，氯膦酸盐脂质体预处理显着减轻DSS诱导的结肠炎，表明巨噬细胞在NaCl促炎活性中起着至关重要的作用。NaCl通过促进白细胞介素（IL）-1、IL-6和小鼠诱导型一氧化氮合酶的表达减轻腹腔巨噬细胞炎症。具体而言，高NaCl浓度促进SGK 1介导的脂多糖和IFN-γ激活的LPMC中的p38磷酸化。结论促炎性巨噬细胞可能在DSS诱导的结肠炎中起重要作用。强调的机制涉及p38/MAPK轴的上调。
AIM To investigate the influence of high salt on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanisms of this effect. METHODS DSS and NaCl were used to establish the proinflammatory animal model. We evaluated the colitis severity. Flow cytometry was employed for detecting the frequencies of Th1, macrophages and Tregs in spleen, mesenteric lymph node and lamina propria. The important role of macrophages in the promotion of DSS-induced colitis by NaCl was evaluated by depleting macrophages with clodronate liposomes. Activated peritoneal macrophages and lamina propria mononuclear cells (LPMCs) were stimulated with NaCl, and proteins were detected by western blotting. Cytokines and inflammation genes were analyzed by enzyme-linked immunosorbent assay and RT-PCR, respectively. RESULTS The study findings indicate that NaCl up-regulates the frequencies of CD11b+ macrophages and CD4+IFN-γ+IL-17+ T cells in lamina propria in DSS-treated mice. CD3+CD4+CD25+Foxp3+ T cells, which can secrete high levels of IL-10 and TGF-β, increase through feedback in NaCl- and DSS-treated mice. Furthermore, clodronate liposomes pretreatment significantly alleviated DSS-induced colitis, indicating that macrophages play a vital role in NaCl proinflammatory activity. NaCl aggravates peritoneal macrophage inflammation by promoting the expressions of interleukin (IL)-1, IL-6 and mouse inducible nitric oxide synthase. Specifically, high NaCl concentrations promote p38 phosphorylation in lipopolysaccharide- and IFN-γ-activated LPMCs mediated by SGK1. CONCLUSION Proinflammatory macrophages may play an essential role in the onset and development of NaCl-promoted inflammation in DSS-induced colitis. The underlining mechanism involves up-regulation of the p38/MAPK axis.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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Tanaka M
影响因子：
30.5
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Denning, Timothy L.;Wang, Yi-Chong;Pulendran, Bali
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Pulendran, Bali