Journal of Applied Biological Chemistry

  • Volume 66
  • /
  • Pages.311-319
  • /
  • 2023
  • /
  • 1976-0442(pISSN)
  • /
  • 2234-7941(eISSN)
The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Phosphorylation of tyrosine-14 on Caveolin-1 enhances lipopolysaccharide-induced inflammation in human intestinal Caco-2 cells

  • Gong Deuk Bae (Lee Gil Ya Cancer and Diabetes Institute, Department of Molecular Medicine, Gachon University) ;
  • Kyong Kim (Department of Food and Nutrition, Eulji University) ;
  • Se-Eun Jang (Department of Food and Nutrition, Eulji University) ;
  • Dong-Jae Baek (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Eun-Young Park (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Yoon Sin Oh (Department of Food and Nutrition, Eulji University)
  • Received : 2023.04.13
  • Accepted : 2023.07.13
  • Published : 2023.12.31
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Abstract

Caveolin-1 (Cav-1) is the main structural component of the caveolae on the plasma membrane, which regulates various cellular processes, including cell growth, differentiation, and endocytosis. Although a recent study demonstrated that Cav-1 might be involved in diabetes-associated inflammation, its exact role in the intestine was unclear. In this study, we examined the intestinal expression of Cav-1 in diabetic conditions. We also investigated its effect on lipopolysaccharide (LPS)-induced inflammation by expressing this protein in human intestinal Caco-2 cells lacking Cav-1. We observed that increased Cav-1 levels and decreased expression of tight junction proteins affected intestinal permeability in high-fat diet-induced diabetic mice. When Caco-2 cells were treated with LPS, Cav-1 enhanced the NF-κB signaling. Moreover, LPS reduced the expression of tight junction proteins while it increased cell-cell permeability and reactive oxygen species generation in Caco-2 cells and this effect was amplified by cav-1 overexpression. LPS treatment promoted phosphorylation of tyrosine-14 (Y14) on Cav-1, and the LPS-induced NF-κB signaling was suppressed in cells expressing non-phosphorylatable Cav-1 (tyrosine-14 to phenylalanine mutant), which reduced intestinal barrier permeability. These results suggest that Cav-1 expression promotes LPS-induced inflammation in Caco-2 cells, and phosphorylation of Y14 on Cav-1 might contribute to the anti-inflammatory response in LPS-induced NF-κB signaling and cell permeability.

Keywords

Acknowledgement

This study was supported by Basic Science Research Program Grant (NRF-2021R1F1A1050949) provided by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT and Future Planning and by a grant from Eulji University in 2022.

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