Related Experiment Video
Updated: Feb 12, 2026
In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
Published on: October 19, 2018
HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial
Ossama Allam1, Suzanne Samarani1, Vikram Mehraj2
1Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of Microbiology, Infectious Diseases & Immunology, University of Montreal, Montreal, Québec, Canada.
Abstract:
Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple context dependent functions. We and others have shown that HIV infection is accompanied by increased circulating levels of IL-18 along with decreased levels of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is also accompanied by intestinal inflammation and decreased intestinal integrity as measured by intestinal permeability, regeneration and repair. However, little is known concerning the relation between high level of IL-18 associated with the viral infection and intestinal permeability. Here we demonstrate that HIV treatment increases production of IL-18 and decreases that of IL-18BP production in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the IEC by activating caspase-1 and caspase-3. It induces epithelial barrier hyperpermeability by decreasing and disrupting both tight and adherens junction proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was also observed in the IEC that were exposed to the cytokine. Moreover IL-18 decreases transepithelial electrical resistance (TEER) in Caco-2 and increases permeability in HT29 monolayers. The cells' treatment with IL-18 causes an increase in the expression of phosphorylated myosin II regulatory light-chain (p-MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in p-MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the levels of the cytokine correlate with those of LPS in the circulation in three different categories of HIV infected patients (HAART-naïve and HAART-treated HIV-infected individuals, and Elite controls) as well as in healthy controls. Collectively, these results suggest that the HIV-induced IL-18 plays a role in increased intestinal permeability and microbial translocation observed in HIV-infected individuals.
Related Concept Videos
01:23Anatomy of the Intestines
Small Intestines
The small intestine is an ~7 meter-long tube with an inner diameter of just 2.5 cm. Since most nutrients are absorbed here, the inner lining of the...
01:15Small Intestine
The small intestine is divided into three main sections - the duodenum, jejunum, and ileum. The duodenum, approximately 25 cm long, is nearest the stomach. It acts as a 'mixing bowl,' where chyme (partially digested food) blends with digestive enzymes from the pancreas and liver. The duodenum's unique...
01:09Large Intestine
The ileocecal sphincter, a mucous membrane fold, guards the opening from the ileum to the large intestine. This valve permits material from the small intestine to pass into the large intestine. Attached to the ileocecal valve is the cecum. This small pouch, approximately 6 cm long, has a twisted, coiled tube known as...
01:23Renewal of Intestinal Stem Cells
01:26Histology of the Large Intestine
The innermost mucosa layer comprises simple columnar epithelium, lamina propria, and muscularis mucosae. This layer is primarily populated with absorptive cells, tasked with water absorption, and goblet cells, responsible for secreting mucus to...
01:27Histology of the Small Intestine
The intestinal lining features transverse folds called circular folds, each housing fingerlike projections known as intestinal villi. These villi are covered by a layer of simple columnar epithelium, also referred to as...