Intestinal barrier function: Molecular regulation and disease pathogenesis
ABSTRACT The intestinal epithelium is a single-cell layer that constitutes the largest and most important barrier against the external environment. It acts as a selectively permeable barrier, permitting the absorption of nutrients, electrolytes, and water while maintaining an effective defense against intraluminal toxins, antigens, and enteric flora. The epithelium maintains its selective barrier function through the formation of complex protein-protein networks that mechanically link adjacent cells and seal the intercellular space. The protein networks connecting epithelial cells form 3 adhesive complexes: desmosomes, adherens junctions, and tight junctions. These complexes consist of transmembrane proteins that interact extracellularly with adjacent cells and intracellularly with adaptor proteins that link to the cytoskeleton. Over the past decade, there has been increasing recognition of an association between disrupted intestinal barrier function and the development of autoimmune and inflammatory diseases. In this review we summarize the evolving understanding of the molecular composition and regulation of intestinal barrier function. We discuss the interactions between innate and adaptive immunity and intestinal epithelial barrier function, as well as the effect of exogenous factors on intestinal barrier function. Finally, we summarize clinical and experimental evidence demonstrating intestinal epithelial barrier dysfunction as a major factor contributing to the predisposition to inflammatory diseases, including food allergy, inflammatory bowel diseases, and celiac disease.
SourceAvailable from: Riccardo Sibilano[Show abstract] [Hide abstract]
ABSTRACT: Mast cells (MCs) are cells of hematopoietic origin that normally reside in mucosal tissues, often near epithelial cells, glands, smooth muscle cells, and nerves. Best known for their contributions to pathology during IgE-associated disorders such as food allergy, asthma, and anaphylaxis, MCs are also thought to mediate IgE-associated effector functions during certain parasite infections. However, various MC populations also can be activated to express functional programs-such as secreting preformed and/or newly synthesized biologically active products-in response to encounters with products derived from diverse pathogens, other host cells (including leukocytes and structural cells), damaged tissue, or the activation of the complement or coagulation systems, as well as by signals derived from the external environment (including animal toxins, plant products, and physical agents). In this review, we will discuss evidence suggesting that MCs can perform diverse effector and immunoregulatory roles that contribute to homeostasis or pathology in mucosal tissues.Mucosal Immunology advance online publication, 11 February 2015; doi:10.1038/mi.2014.131.Mucosal Immunology 02/2015; DOI:10.1038/mi.2014.131 · 7.54 Impact Factor
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ABSTRACT: Tight junctions (TJs) maintain the intestinal mucosal barrier, dysfunction of which plays a vital role in the pathophysiology of a variety of gastrointestinal disorders. Previously, we have shown that L. reuteri I5007 maintained the gut epithelial barrier in newborn piglets. Here we aimed to decipher the influence of L. reuteri I5007 on tight junction (TJ) protein expression both in vivo and in vitro. We found that L. reuteri I5007 significantly increased the protein abundance of intestinal epithelial claudin-1, occludin and zonula occluden-1 (ZO-1) in newborn piglets (orally administrated with 6 × 10(9) CFU of L. reuteri I5007 daily for 14 days). In vitro, treatment with L. reuteri I5007 alone maintained the transepithelial electrical resistance (TEER) of IPEC-J2 cells with time. In addition, IPEC-J2 cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) for 1, 4, 8, 12 or 24 h, following pre-treatment with L. reuteri I5007 or its culture supernatant for 2 h. The results showed that LPS time-dependently induced (significantly after 4 or 8 h) the expression of TNF-α and IL-6, and decreased TJ proteins, which was reversed by pre-treatment of L. reuteri I5007 or its culture supernatant. L. reuteri I5007 had beneficial effects on the expression of TJ proteins in newborn piglets and the in-vitro results showed this strain had a positive effect on TEER of cells and inhibited the reduction of TJ proteins expression induced by LPS. These findings indicated L. reuteri I5007 may have potential roles in protection TJ proteins in TJ-deficient conditions.BMC Microbiology 12/2015; 15(1). DOI:10.1186/s12866-015-0372-1 · 2.98 Impact Factor
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ABSTRACT: Necrotizing enterocolitis is an acute inflammatory disease, which primarily affects preterm infants, and is a leading cause of morbidity and mortality in the neonatal intensive care unit. Unfortunately, necrotizing enterocolitis can be difficult to distinguish from other diseases and clinical conditions especially during the early course of the disease. This diagnostic uncertainty is particularly relevant to clinical evaluation and medical management and potentially leads to unnecessary and extended periods of cessation of enteral feedings and prolonged courses of parenteral nutrition and antibiotics. Biomarkers are molecular indicators of a disease process, diagnosis, prognosis and can be used to monitor the effects of disease management. Historically, there has been a paucity of reliable and robust biomarkers for necrotizing enterocolitis. However, several studies have recently identified promising biomarkers. Noninvasive samples for biomarker measurement are preferred and may have certain advantages in the preterm infant. In this review article, we focus on recent exciting and promising discoveries in noninvasive biomarkers for necrotizing enterocolitis.The Journal of perinatal & neonatal nursing 01/2015; 29(1):69-80. DOI:10.1097/JPN.0000000000000082 · 1.01 Impact Factor