Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions.
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-1LCP 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.
College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China. bfli@ouc.edu.cn and Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Qianru
Q
Chen
Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Oliver
O
Chen
Department of Food Science, Faculty of Food Engineering, State University of Campinas (UNICAMP), Brazil.
Isabela M
IM
Martins
College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China. bfli@ouc.edu.cn.
Hu
H
Hou
College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China. bfli@ouc.edu.cn.
Xue
X
Zhao
Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Jeffrey B
JB
Blumberg
College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China. bfli@ouc.edu.cn.
Bafang
B
Li
D000818:Animals; D018938:Caco-2 Cells; D003094:Collagen / Q000008:administration & dosage / Q000737:chemistry*; D029941:Fish Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D005399:Fishes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000187:drug effects* / Q000276:immunology; D062793:Occludin / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D012867:Skin / Q000737:chemistry*; D019108:Tight Junctions / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D029941:Fish Proteins; D062793:Occludin; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen