Sharmila G R, Venkateswaran G
Academy of Scientific and Innovative Research, CSIR-Central Food Technological Research Institute, Mysuru 570020, India; Microbiology and Fermentation Technology Department, CSIR-Central Food Technological Research Institute, Mysuru 570020, India.
Academy of Scientific and Innovative Research, CSIR-Central Food Technological Research Institute, Mysuru 570020, India; Microbiology and Fermentation Technology Department, CSIR-Central Food Technological Research Institute, Mysuru 570020, India.
Biochem Biophys Res Commun. 2017 Sep 16;491(2):455-462. doi: 10.1016/j.bbrc.2017.07.054. Epub 2017 Jul 11.
Bacillopeptidase is a serine peptidase, known for its fibrinolytic activity. However, a very little information is known about its in vivo inflammatory and/or anti-inflammatory properties. Thus, to understand whether bacillopeptidase incorporation can regulate pancreatitis or not, the cerulein-induced pancreatitis model was used, and the role of bacillopeptidase on pancreatitis was studied. In this study, 46 kDa protein was purified from Bacillus subtilis and identified as bacillopeptidase CFR5 (BPC) through MS/MS analysis. The nutritional prophylactic group was orally fed with two doses of BPC (100 μg/Kg/BW of rat) 6 h before cerulein administration and analyzed for its effect on intestine and pancreas inflammation, cytokines, and pancreatitis marker gene expression. BPC administration significantly reduced the severity of pancreatitis by decreasing serum amylase, lipase, pancreatic edema and myeloperoxidase activity. The pretreatment with BPC suppressed the pancreatic pro-inflammatory and inflammatory cytokines production including IL-6, IL-1β, TNF-α, IL-2, IL-4, IL-5, IL-10, and IL-13 in both pancreas and serum samples. Moreover, BPC supplementation restored pancreatitis mediated disruption of intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin), antimicrobial peptides (DEFB1, CRAMP), MUC-2, TFF3 expression and by enhancing SCFA's production. Pretreatment with BPC suppressed the intestinal inflammation with reduced cytokines production in the colon and ileal region of cerulein-induced pancreatitis. Thus, BPC based pretreatment protocol is a novel intervention to prevent acute pancreatitis.
芽孢杆菌肽酶是一种丝氨酸肽酶,以其纤溶活性而闻名。然而,关于其体内炎症和/或抗炎特性的信息却知之甚少。因此,为了了解芽孢杆菌肽酶的掺入是否能调节胰腺炎,我们使用了雨蛙肽诱导的胰腺炎模型,并研究了芽孢杆菌肽酶在胰腺炎中的作用。在本研究中,从枯草芽孢杆菌中纯化出46 kDa的蛋白质,并通过串联质谱分析鉴定为芽孢杆菌肽酶CFR5(BPC)。营养预防组在给予雨蛙肽前6小时口服两剂BPC(100 μg/Kg/大鼠体重),并分析其对肠道和胰腺炎症、细胞因子以及胰腺炎标志物基因表达的影响。给予BPC可通过降低血清淀粉酶、脂肪酶、胰腺水肿和髓过氧化物酶活性,显著减轻胰腺炎的严重程度。BPC预处理抑制了胰腺和血清样本中促炎和炎性细胞因子的产生,包括IL-6、IL-1β、TNF-α、IL-2、IL-4、IL-5、IL-10和IL-13。此外,补充BPC可通过上调紧密连接蛋白(ZO-1、闭合蛋白)、抗菌肽(DEFB1、CRAMP)、MUC-2、TFF3的表达以及增强短链脂肪酸的产生,恢复胰腺炎介导的肠道屏障完整性破坏。BPC预处理抑制了雨蛙肽诱导的胰腺炎结肠和回肠区域的肠道炎症,减少了细胞因子的产生。因此,基于BPC的预处理方案是预防急性胰腺炎的一种新干预措施。