Curcumin Mitigates TNFalpha-Induced Caco-2 Cell Monolayer Permeabilization Through modulation of NF-kappaB, ERK1/2 and JNK Pathways

Mol Nutr Food Res. 2022 Feb 19:e2101033. doi: 10.1002/mnfr.202101033. Online ahead of print.

ABSTRACT

SCOPE: This work studied the capacity of curcumin to inhibit TNFα-induced inflammation, oxidative stress, and loss of intestinal barrier integrity, characterizing the underlying mechanisms.

METHODS AND RESULTS: Caco-2 cell monolayers were incubated with TNFα (10 ng/ml), in the absence or presence of curcumin. TNFα caused an increase in interleukin (IL)-6 and IL-8 release which was inhibited by curcumin in a dose-dependent manner (IC50 = 3.4 μM for IL-6). Moreover, TNFα led to: i) increased ICAM-1 and NLRP3 expression; ii) increased cell monolayer permeability and decreased levels of tight junction proteins; iii) increased cellular and mitochondrial oxidant production; iv) decreased mitochondrial membrane potential and complex I-III activity; v) activation of redox-sensitive pathways, i.e., NF-κB, ERK1/2 and JNK; and vi) increased MLCK expression and phosphorylation levels of MLC. Curcumin (2-8 μM) inhibited all these TNFα-triggered undesirable outcomes, mostly showing dose-dependent effects.

CONCLUSION: The inhibition of NF-κB, ERK1/2 and JNK activation could be in part involved in the capacity of curcumin to mitigate intestinal inflammation, oxidant production, activation of redox-sensitive pathways, and prevention of monolayer permeabilization. These results support an action of dietary curcumin in sustaining gastrointestinal tract physiology. This article is protected by copyright. All rights reserved.

PMID:35182412 | DOI:10.1002/mnfr.202101033