Abstract
The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level.
Highlights
Impairment of the intestinal barrier is involved in the pathogenesis of inflammatory bowel disease (IBD) [1]
Tumor necrosis factor alpha (TNFα) is the cytokine most often associated with epithelial tight junction (TJ) dysregulation and intestinal barrier impairment [4,5,6], but several other cytokines, such as IL-13 [7], interferon gamma (IFN-γ) [8], IL-6 [9], or IL-1beta (IL-1β) [10] have been involved
The elucidation of MAPK role needs further investigation, including the effect of suppression of their activity through genetic or pharmacological means. Both CAT and procyanidin B2 (PB2) lowered the expression of ZO-1, making it not completely surprising that they do not counteract the fall in the expression of the protein caused by inflammation
Summary
Impairment of the intestinal barrier is involved in the pathogenesis of inflammatory bowel disease (IBD) [1]. The effects and mechanisms behind the protective role of flavan-3-ols on the onset of IBD may be related to different pathways, as it has been recently reviewed [27] Despite their many limitations, in vitro cell models still represent a useful tool to predict the effects mediated by natural compounds on several functional end points, such as epithelial barrier permeability. Alteration of TEER can be experimentally induced in intestinal cell monolayers through the addition of inflammatory cytokines, used individually or as a mixture, or of other inflammatory stimuli to the basolateral side of the cell system [32] This approach has been successfully used to document the protective effects of phyto-compounds on epithelial integrity under inflammatory conditions [31,33]. We have used a similar approach to investigate if CAT or PB2 pretreatment mitigates the impairment of intestinal barrier function due to inflammatory stimuli
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
