Caco-2 based in vitro models for the screening of anti-inflammatory drugs

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Lourdes Gombau | R&D Director
25 January 2023

Inflammatory Reactions of the Intestinal Tract

Inflammatory reactions of the intestinal tract are the result of a combination of hereditary, genetic and/or environmental factors that have been clustered in the inflammatory bowel disease (IBD), a term that describe disorders that involve chronic inflammation of the digestive tract. The release of a complex network of mediators (cytokines, chemokines, growth factors, adhesion molecules and neuropeptides) produced by the intestinal epithelial cells as well as by immune-related cells and other cell types of the lamina propia are the major features of this inflammatory process.

Cell-Based Assays for Anti-Inflammatory Drugs

The use of cell-based assays that can provide valuable insights into the efficacy of anti-inflammatory drugs to treat intestinal inflammation requires a cell model which closely resembles the in vivo IDB. Caco-2 based models, either those only including the absorptive cell phenotype (Caco-2) or the co-cultures of enterocytes and mucus-secreting cells (Caco-2/HT29 MTX) have been shown to be useful to conduct these kinds of studies since they are both responsive to pro-inflammatory stimulation, producing a wide range of intestinal mediators and increasing the paracellular permeability.

Flavanols, flavonols and anthocyanidins obtained from natural products such as plant and wine extracts are some examples of compounds that have been reported to have anti-inflammatory properties on Caco-2 based models previously exposed to inflammatory mediators (TNFα, IL1β, LPS). They prevent or reduce the synthesis and release of the inflammatory cytokines IL-6 and IL-8 and protect from intestinal permeability alterations. Chlorogenic acid, a polyphenol found in coffee and black tea has also been described to inhibit TNFα- and H2O2-induced IL-8 production in Caco-2 cells while a Bubalus bubalis milk-derived peptide help to restore the intestinal epithelium integrity in inflamed Caco-2 cells and in a dinitrobenzene sulfonic acid (DNBS) mice model of colitis.

ReadyCell has available CacoGoblet to assay compounds inflammatory properties. This ready-to-use cell-based model is established with differentiated human colorectal carcinoma cells (Caco-2 and HT29 cells) that mimic the morphological and functional properties of the intestinal barrier in vivo. The model is preplated and differentiated on transwell insert plates and delivered worldwide by means of our patented gel-like Shipping Medium®.

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