The physical and immunological properties of the human intestinal epithelial barrier in ageing are largely unknown. Ileal biopsies from young (7-12 years), adult (20-40y) and ageing (67-77y) individuals not showing symptoms of gastrointestinal pathologies were used to assess levels of inflammatory cytokines, barrier integrity, and cytokine production in response to microbial challenges. Increased expression of IL-6, but not IFNg, TNF-a and IL- 1b was observed during ageing; further analysis showed that CD11c+ dendritic cells (DCs) are one of the major sources of IL-6 in the ageing gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of Claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex-vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of Zonula occludens-1, Occludin and Junctional-Adhesion Molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production to different microbial stimuli was assessed in a polarized in vitro organ culture. IL-8 production in response to flagellin declined progressively with age although the expression and distribution of TLR-5 on intestinal epithelial cells remained unchanged. Also, flagellininduced production of IL-6 was less pronounced in ageing. In contrast, TNF-a production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL- 6 and expression of Claudin 2. These data suggested that ageing affects properties of the intestinal barrier likely to impact on ageassociated disturbances both locally and systemically.
Scheda prodotto non validato
Scheda prodotto in fase di analisi da parte dello staff di validazione
|Titolo:||Age-associated modifications of intestinal permeability and innate immunity in human small intestine|
|Citazione:||Man, A.L., Bertelli, E., Rentini, S., Regoli, M., Briars, G., Marin, M., et al. (2015). Age-associated modifications of intestinal permeability and innate immunity in human small intestine. CLINICAL SCIENCE, 129(7), 515-527.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
File in questo prodotto: