TLR2, TLR3, and TLR4 activation specifically alters the oxidative status of intestinal epithelial cells

Abstract

Intestinal inflammatory diseases are the result of multiple processes, including mucosal oxidative stress and perturbed homeostasis between commensal bacteria and mucosal immunity. Toll-like receptors (TLRs) recognize molecular-associated microorganisms' patterns and trigger innate immunity responses contributing to intestinal homeostasis and inflammatory responses. However, TLRs effects on redox balance in intestinal mucosa remain unknown. Therefore, the present study analyzes the effect of TLR2, TLR3, and TLR4 on both oxidative damage of lipids and proteins, and the activity of antioxidant enzymes in enterocyte-like Caco-2 cells. The results show that the activation of these TLRs increased lipid and protein oxidation levels; however, the effect on the antioxidant enzymes activity is different depending on the TLR activated. These results suggest that the activation of TLR2, TLR3, and TLR4 might affect intestinal inflammation by not only their inherent innate immunity responses, but also their pro-oxidative effects on intestinal epithelial cells.

TLR2 deficiency attenuates skeletal muscle atrophy in mice

“…The activation of TLR2 increases inflammatory cytokine levels and induces lipid and protein oxidation in non-immune cells, such as intestinal epithelial cells and cardiomyocytes [14,15]. Accordingly, TLR2 deficiency suppresses the upregulation of cytokine expression and oxidative stress induced by pro-oxidants in the liver [16,17].…”

The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair

“…Finally, poly(IC) has also been reported to regulate gut permeability and induce oxidative stress in an epithelial cell line [77,78]. Thus, TLR3 signalling in the epithelium seems to contribute both to host-protective epithelial cell shedding during pathogen challenge, as well as cell damage and injury that can be detrimental to the host.…”

NOD2 Modulates Serotonin Transporter and Interacts with TLR2 and TLR4 in Intestinal Epithelial Cells

“…We have used these human epithelial cells as in vitro model, since previous works have demonstrated that this cell line expresses SERT and innate immunity receptors, thus being an optimal intestinal model for analyzing SERT [24] and PRRs [12,25]. Caco2/TC7 cells were cultured at 37°C in an atmosphere of 5% CO 2 with highglucose DMEM, supplemented with 2 mM glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin, 1% nonessential amino acids and 20% heat-inactivated fetal bovine serum (FBS) from Life Technologies (Carlsbad, CA, USA).…”

“…Pattern recognition receptors (PRRs) are innate immune components, which mainly involves Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs). PRRs are expressed in intestinal epithelial cells [11,12] and are able to recognize microbial-associated molecular patterns (MAMPs) to develop either inflammatory or tolerance responses [13]. In this context, several studies have reported that numerous PRRs, as TLR2, TLR4 [14] and NOD2 [15], seem to be implicated in IBD due to the dysfunctional recognition of commensal microbiota [16].…”