Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice.
Cathelicidin-related antimicrobial peptide modulates the severity of acute pancreatitis in mice.
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导管素相关抗菌肽调节小鼠急性胰腺炎的严重程度
DOI：
10.3892/mmr.2016.5008
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Deng YY;Shamoon M;He Y;Bhatia M;Sun J
本研究旨在探讨小鼠导管素相关抗菌肽（CRAMP）对实验性急性胰腺炎（AP）的免疫调节作用。 AP是一种以急性腹部炎症为特征的常见临床病症。先天免疫细胞和介质与 AP 的发病机制有着内在的联系。 Cathelicidins 是先天免疫衍生的抗菌肽，对各种宿主细胞发挥免疫调节作用。然而，导管素如何参与并调节 AP 的严重程度和炎症反应仍不清楚。在本研究中，小鼠 CRAMP 基因缺陷的 cnlp−/− 小鼠及其野生型 C57BL/6J 同窝小鼠通过每小时多次注射超大剂量的雨蛙素来诱导 AP。进行血清淀粉酶水平、胰髓过氧化物酶活性和组织学检查以确定疾病的严重程度和炎症细胞因子的水平。随后在对照小鼠、患有 AP 的 cnlp−/− C57BL/6J 小鼠和患有 AP 的野生型 C57BL/6J 小鼠中评估疾病严重程度和炎症标志物。结果表明，与野生型小鼠相比，cnlp−/− 小鼠在 AP 诱导后表现出更严重的表型和炎症反应，血清淀粉酶水平增加、胰髓过氧化物酶释放和早期炎症介质肿瘤坏死因子-α 产生证明了这一点。组织学检查证实 CRAMP 缺乏使胰腺炎症状况恶化。这些结果表明 CRAMP 可能被认为是小鼠实验性 AP 中的一种新型调节介质。
The present study aimed to investigate the immunomodulatory effects of mouse cathelicidin-related antimicrobial peptide (CRAMP) on experimental acute pancreatitis (AP). AP is a common clinical condition characterized by acute abdominal inflammation. Innate immune cells and mediators are intrinsically linked to the pathogenesis of AP. Cathelicidins are innate immunity-derived antimicrobial peptides that exert immunomodulatory effects on various host cells. However, how cathelicidins are involved and modulate the severity and inflammatory responses of AP remains unclear. In the present study, the mouse CRAMP gene-deficient cnlp−/− mice and their wild-type C57BL/6J littermates were induced with AP by multiple hourly injections of supramaximal doses of caerulein. Serum amylase levels, pancreatic myeloperoxidase activity and histological examination were performed in order to determine the disease severity and the levels of inflammatory cytokines. Disease severity and inflammatory markers were subsequently evaluated in the control mice, cnlp−/− C57BL/6J mice with AP, and wild-type C57BL/6J mice with AP. The results demonstrated that cnlp−/− mice exhibited a more severe phenotype and inflammatory response following AP induction compared with the wild-type mice, as evidenced by increased serum amylase levels, pancreatic myeloperoxidase release, and early inflammatory mediator tumor necrosis factor-α production. Histological examination confirmed that CRAMP deficiency worsened the pancreatic inflammatory condition. These results indicate that CRAMP may be considered a novel modulatory mediator in mouse experimental AP.