College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China.
Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Food Funct. 2017 Mar 22;8(3):1144-1151. doi: 10.1039/c6fo01347c.
Dysfunction of the intestinal barrier plays a key role in the pathogenesis of inflammatory bowel disease (IBD) and multiple organ failure. The effect of Alaska pollock skin-derived collagen and its 3 tryptic hydrolytic fractions, HCP (6 kDa retentate), MCP (3 kDa retentate) and LCP (3 kDa permeate) on TNF-α induced barrier dysfunction was investigated in Caco-2 cell monolayers. TNF-α induced barrier dysfunction was significantly attenuated by the collagen and its peptide fractions, especially LCP, compared to TNF-α treated controls (P < 0.05). Compared to a negative control, 24 h pre-incubation with 2 mg mL LCP significantly alleviated the TNF-α induced breakdown of the tight junction protein ZO-1 and occludin and inhibited MLC phosphorylation and MLCK expression. The activation of NFκB and Elk-1 was suppressed by LCP. Thus, collagen peptides may attenuate TNF-α induced barrier dysfunction of Caco-2 cells by inhibiting the NFκB and ERK1/2-mediated MLCK pathway with associated decreases in ZO-1 and occludin protein expression.
肠道屏障功能障碍在炎症性肠病（IBD）和多器官衰竭的发病机制中起着关键作用。研究了阿拉斯加狭鳕皮胶原蛋白及其 3 种胰蛋白酶水解产物 HCP（6 kDa 截留物）、MCP（3 kDa 截留物）和 LCP（3 kDa 透过物）对 Caco-2 细胞单层中 TNF-α诱导的屏障功能障碍的影响。与 TNF-α 处理对照组相比，胶原蛋白及其肽片段，尤其是 LCP，可显著减轻 TNF-α诱导的屏障功能障碍（P < 0.05）。与阴性对照相比，24 h 用 2 mg mL LCP 预孵育可显著减轻 TNF-α诱导的紧密连接蛋白 ZO-1 和闭合蛋白的破坏，并抑制 MLC 磷酸化和 MLCK 表达。LCP 抑制 NFκB 和 Elk-1 的激活。因此，胶原蛋白肽可能通过抑制 NFκB 和 ERK1/2 介导的 MLCK 途径，以及相关的 ZO-1 和闭合蛋白表达减少，减轻 TNF-α诱导的 Caco-2 细胞屏障功能障碍。
