Modulation of intestinal barrier function by glucocorticoids: Lessons from preclinical models. (March 2022)

• Record Type: Journal Article
• Authors: Tena-Garitaonaindia, Mireia; Arredondo-Amador, María; Mascaraque, Cristina; Asensio, Maitane; Marin, Jose J.G.; Martínez-Augustin, Olga; Sánchez de Medina, Fermín
• Is Part Of: Pharmacological research. Volume 177(2022)
• Publication Date: 2022-03
• Subjects: DSS dextran sulfate sodium -- FITC fluorescein isotiocyanate -- GC glucocorticoid -- GR glucocorticoid receptor -- IBD inflammatory bowel disease -- IBF intestinal barrier function -- IEC intestinal epithelial cells -- MKP-1 MAPK phosphatase 1 -- MLCK myosin like chain kinase -- TEER transepithelial electrical resistance -- ZO zonulae occludens; Glucocorticoid -- Intestinal barrier function -- IgA -- Colitis -- Stress; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106056
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Glucocorticoids (GCs) are widely used drugs for their anti-inflammatory and immunosuppressant effects, but they are associated with multiple adverse effects. Despite their frequent oral administration, relatively little attention has been paid to the effects of GCs on intestinal barrier function. In this review, we present a summary of the published studies on this matter carried out in animal models and cultured cells. In cultured intestinal epithelial cells, GCs have variable effects in basal conditions and generally enhance barrier function in the presence of inflammatory cytokines such as tumor necrosis factor (TNF). In turn, in rodents and other animals, GCs have been shown to weaken barrier function, with increased permeability and lower production of IgA, which may account for some features observed in stress models. When given to animals with experimental colitis, barrier function may be debilitated or strengthened, despite a positive anti-inflammatory activity. In sepsis models, GCs have a barrier-enhancing effect. These effects are probably related to the inhibition of epithelial cell proliferation and wound healing, modulation of the microbiota and mucus production, and interference with the mucosal immune system. The available information on underlying mechanisms is described and discussed. Graphical Abstract: ga1