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Ethanol‐Induced CXC‐Chemokine Synthesis and Barrier Dysfunction in Intestinal Epithelial Cells
Author(s) -
Kishikawa Hiroshi,
Miura Soichiro,
Nishida Jiro,
Nakano Masaru,
Hirano Erika,
Sudo Nao,
Morishita Tetsuo,
Ishii Hiromasa
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000192299.63463.50
Subject(s) - barrier function , secretion , chemokine , immune system , tight junction , chemistry , interleukin 8 , ethanol , medicine , intestinal epithelium , chromosomal translocation , epithelium , endocrinology , immunology , biology , inflammation , biochemistry , pathology , microbiology and biotechnology , gene
A bstract : Background: Ethanol exposure contributes to infectious complications in burn and trauma patients through a process known as “bacterial translocation.” Two major factors, 1) physical disruption of the intestinal mucosal barrier and 2) suppression of immune defense, explain this phenomenon. However, little information is available concerning the immune mechanisms of ethanol‐induced bacterial translocation. In this study we investigated the effect of physiological concentrations of ethanol on immune function, especially on CXC‐chemokine secretion, neutrophil migration, and barrier function in the small intestine Methods: A rat small intestinal intestinal cell line (IEC‐18 cells) was exposed to 50–500 mM ethanol for 24 hr with or without IL‐1β. Secretion of CXC chemokines (GRO/CINC‐1 and MIP‐2) was measured by ELISA assay, and barrier dysfunction was assessed by the apical‐to‐basolateral flux of HRP‐dextran. Neutrophil transmigration was assessed by enzyme histochemistry (AS‐D chloroesterase staining) Results: Exposure to ethanol concentrations of 200mM and over increased GRO/CINC‐1 secretion, and MIP‐2 secretion increased at 500 mM. Administration of ethanol in combination with IL‐1β had no additive effect on the release of GRO/CINC‐1 and MIP‐2. Exposure of IEC‐18 monolayers to ethanol resulted in a dose‐dependent increase in peameability but IL‐1β had no effect on barrier function. Ethanol had no effect on neutrophil migration in enzyme histochemistry analysis Conclusions: The above observations suggest that ethanol induced physical disruption of the intestine but not neutrophil transmigration is the main cause of the bacterial translocation that leads to bacteremia and endotoxemia in alcoholics.