Intestinal Epithelial Signaling

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The Intestinal Epithelium as A Model in Cell Biology

The intestinal epithelium is a particularly suitable system for studying the basic processes of cell differentiation. The balance and competition between chemical or physical signals enable the coordination of intestinal epithelial cell proliferation, localization, migration, and differentiation to maintain tissue homeostasis. Disruption of this balance can lead to alterations in the epithelium and the development of several pathologies, including inflammatory bowel disease (IBD) or colorectal cancer. In vitro models have been widely used in basic research or drug testing and toxicology.

Current Approaches to Study the Intestinal Epithelium In Vitro

The epithelial cells commonly used for in vitro studies are cell lines derived from colorectal cancer. These cell lines are highly proliferative and relatively easy and inexpensive to use, making them very useful for mechanistic studies, toxicological analysis, or high-throughput screening methods. The Caco-2 and HT-29 cell systems provide excellent models for studying enterocyte and mucoid function. These established cell lines are also widely used as model systems for the study of biological pathways in the development and treatment of cancer.

  • The Caco-2 Cell Line

Caco-2 cells were derived from well-differentiated tumors. They represent the most widely used model for drug permeability and absorption experiments, as well as for differentiation. This cell line is of potential interest for studies related to molecular events associated with cell polarity, enzyme biogenesis, and transport properties. The regulation of intestinal epithelial differentiation by extracellular matrix proteins has been studied, particularly using the Caco-2 cell line.

  • The HT-29 Cell Line

The human HT-29 adenocarcinoma cell line is considered a pluripotent intestinal cell line. Under glucose supply and in the presence of serum, HT-29 cells are undifferentiated. However, HT-29 cells can express various differentiation characteristics under the influence of medium changes or differentiation inducers.

Current in vitro models to study the intestinal epithelium.Fig.1 Current in vitro models to study the intestinal epithelium. (Creff, 2021)

Modulation of Cytokines by Probiotics

Immunomodulatory effects of different species of probiotics were shown both in vitro and in vivo by their contribution to the induction or inhibition of specific cytokines, usually in a way of antagonizing the effects introduced by pathogens against the health of the intestine. Many studies have focused on the regulation of IL-8 secretion or gene expression by probiotics. Investigating how probiotics influence cytokine networks and cytokine formation behaviors that are highly correlated with the initiation of adaptive immune responses is necessary to gain insight into the potentially beneficial effects of probiotics in promoting gut health.

Intestinal epithelial cells mediate the crosstalk between gut microbes and host immunity.Fig.2 Intestinal epithelial cells mediate the crosstalk between gut microbes and host immunity. (Okumura, 2017)

Intestinal Epithelial Signaling Assays at Creative Biolabs

Probiotics are considered a promising therapy against GI inflammation. Most studies preferred to use "stimulated" cell models which mimic a situation of infection or inflammation to test whether certain strains of probiotics have an alleviating potential by measuring the level of target cytokines.

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  1. Creff, J.; et al. In vitro models of intestinal epithelium: toward bioengineered systems. Journal of Tissue Engineering. 2021, 12: 2041731420985202.
  2. Okumura, R.; Takeda, K. Roles of intestinal epithelial cells in the maintenance of gut homeostasis. Experimental & molecular medicine. 2017, 49(5): e338-e338.

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