Modulation of Barrier Function of Small Intestinal Epithelial Cells by Lamina Propria Fibroblasts in Response to Lipopolysaccharide: Possible Role of TNFα in Inducing Barrier Dysfunction

Publisher Website
Google Scholar
Abstract
Recent evidence suggests an interaction between immune, enteric neural and fibroblasts in the regulation of intestinal function. Earlier, we have reported that lipopolysaccharide (LPS) induced cell proliferation, collagen synthesis and production of proinflammatory mediators in lamina propria fibroblasts. In this report, we investigated the change in transepithelial resistance (TER) as a marker of epithelial barrier function by lipopolysaccharide (LPS) and its modulation by human small intestinal lamina propria fibroblasts (HSILPF). Epithelial cells incubated with LPS alone did not show any change in the TER at any concentration or prolonged exposure. However, co‐cultivation of epithelial cells with lamina propria fibroblasts which had been exposed to LPS resulted in a rapid decrease in TER by 2 hr. The decrease in the TER was continued till 8 hr followed by returning to the basal level by 24 hr. The supernatant of LPS‐treated HSILPF was less effective in causing a fall in the TER than HSILPF itself. The fall in TER was accompanied by loosening of tight junctions as depicted by increased penetration of horse radish peroxidase (HRP) across the epithelial cells from the apical to the basal side. Increased incorporation of 3[H]thymidine (tritiated thymidine) in epithelial cells was observed at 48 hr in the presence of LPS‐treated HSILPF. The decrease in TER during the early time period in epithelial cells was abrogated to 70% by incubating the LPS‐treated HSILPF and the conditioned medium of LPS‐treated HSILPF with anti‐TNFα antibody, and not with antibody to other cytokines like IL1α, IL1β, IL6 and IL8. Overall, these results suggest that TNFα produced by HSILPF in response to LPS as a soluble form cause a decrease in the TER and loosening of tight junctions, and such early changes in the epithelial barrier may contribute to local inflammation in the gut.