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GYY4137 ameliorates intestinal barrier injury in a mouse model of endotoxemia
- Source :
- Biochemical Pharmacology. 118:59-67
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Intestinal barrier injury has been reported to play a vital role in the pathogenesis of endotoxemia. This study aimed to investigate the protective effect of GYY4137, a newly synthesized H2S donor, on the intestinal barrier function in the context of endotoxemia both in vitro and in vivo. Caco-2 (a widely used human colon cancer cell line in the study of intestinal epithelial barrier function) monolayers incubated with lipopolysaccharide (LPS) or TNF-α/IFN-γ and a mouse model of endotoxemia were used in this study. The results suggested that GYY4137 significantly attenuated LPS or TNF-α/IFN-γ induced increased Caco-2 monolayer permeability. The decreased expression of TJ (tight junction) proteins induced by LPS and the altered localization of TJs induced by TNF-α/IFN-γ was significantly inhibited by GYY4137; similar results were obtained in vivo. Besides, GYY4137 promoted the clinical score and histological score of mice with endotoxemia. Increased level of TNF-α/IFN-γ in the plasma and increased apoptosis in colon epithelial cells was also attenuated by GYY4137 in mice with endotoxemia. This study indicates that GYY4137 preserves the intestinal barrier function in the context of endotoxemia via multipathways and throws light on the development of potential therapeutic approaches for endotoxemia.
- Subjects :
- Lipopolysaccharides
Male
0301 basic medicine
Cell Membrane Permeability
Lipopolysaccharide
Morpholines
Apoptosis
Context (language use)
Biology
Pharmacology
Protective Agents
Biochemistry
Tight Junctions
Interferon-gamma
Random Allocation
03 medical and health sciences
chemistry.chemical_compound
Gastrointestinal Agents
Intestinal mucosa
In vivo
Electric Impedance
Animals
Humans
Intestinal Mucosa
Barrier function
Gastrointestinal agent
Tight Junction Proteins
Tight junction
Tumor Necrosis Factor-alpha
Organothiophosphorus Compounds
Endotoxemia
Mice, Inbred C57BL
Disease Models, Animal
Enterocytes
030104 developmental biology
Gene Expression Regulation
chemistry
Caco-2
Immunology
lipids (amino acids, peptides, and proteins)
Caco-2 Cells
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....54fde5c870f54a0dff2fb62052145d1b