Protective effects of curcumin on TNF induced Caco-2 cell monolayers permeabilization

IGLESIAS, DARIO E.; FRAGA, CESAR G.; OTEIZA, PATRICIA I.; CREMONINI, ELEONORA

Congreso; Society for Redox Biology and Medicine; 2020

Intestinal epithelium structure and function can be affected by exposure to the pro-inflammatory cytokine tumor necrosis factor alpha (TNF), which triggers local inflammation. Intestinal inflammation involves a cycle of oxidative stress, activation of redox-sensitive transcription factors, and barrier permeabilization. This latter exacerbates local inflammatory conditions and can lead to systemic inflammation and its associated co morbidities. Dietary polyphenols can protect the intestinal epithelium by modulating inflammation and, in turn, barrier integrity. In this sense, curcumin was reported to have several health beneficial properties, including intestinal anti-inflammatory effects. This work studied the mechanisms by which curcumin inhibits TNF induced inflammation, oxidative stress, and loss of barrier integrity, using Caco-2 cells differentiated into an intestinal epithelial cell monolayer. Caco-2 cell monolayers were incubated with TNF (10 ng/ml), in the absence or presence of different curcumin concentrations. As a consequence of TNF addition, interleukin (IL) 6 and 8 were released into the medium. The release of these pro-inflammatory cytokines was inhibited by curcumin in a dose-dependent manner (IC50=3.4 M for IL-6). Moreover, TNF led to: i) increased ICAM-1 and NLRP3 expression; ii) increased cellular oxidant production; iii) loss of monolayer permeability and decreased levels of tight junction proteins; iv) activation of the redox-sensitive pathways NF-B, ERK1/2 and JNK; v) decreased mitochondrial membrane potential; and vi) increased MLCK gene expression and MLC phosphorylation. Curcumin (2-8 M) was able to inhibit all these TNF-triggered adverse effects, in general showing a dose-dependent profile. Curcumin?s capacity to inhibit NF-B, ERK1/2 and JNK activation, which consequently breaks the self-feeding cycle of inflammation, oxidative stress, redox-sensitive signaling pathways activation and monolayer permeabilization, can partially explain the protective effects of this polyphenol at the gastrointestinal tract.