Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha

Satsu, Hideo; Ishimoto, Yoko; Nakano, Tomoko; Mochizuki, Tetsunosuke; Iwanaga, Toshihiko; Shimizu, Makoto

doi:10.1016/j.yexcr.2006.08.018

Cited by 89 publications

(92 citation statements)

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“…Interestingly, this interaction did not disrupt the intercellular barrier of the tight junctions as shown by uncompromised TEER value measurements. Other studies have shown that THP-1 cells co-cultivated with Caco-2 cells induced epithelial cell death mainly due to TNF-a secretion by THP-1 cells (Satsu et al, 2006). However, this was not observed in our system.…”

Section: Discussioncontrasting

confidence: 83%

A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials

et al. 2015

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CitationA 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials. AbstractOral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO 2 , NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1b, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO 2 or Au NPs. But once inflamed with IL-1b, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation.

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Section: Discussioncontrasting

confidence: 83%

A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials

et al. 2015

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“…Co-culturing with other cells can also expand the usefulness of the IEC cell lines. [21][22][23][24] Some of the studies done by ourselves using IEC cell lines are introduced here. These include (i) mechanism studies on the intestinal absorption of functional food substances, (ii) analyses of food substances that regulate the intestinal absorption of nutrients, (iii) analysis of food substances that regulate enzymes for intestinal detoxification and metabolism, and (iv) analysis of food substances that regulate intestinal inflammation.…”

Section: Cell-based In Vitro Assay For Iec Functionsmentioning

confidence: 99%

“…This model is a co-culture system with intestinal epithelial cells and macrophage-like cells. 24) Briefly, human intestinal Caco-2 cells were monolayer-cultured for 2 weeks on a semi-permeable membrane equipped with a culture insert. Human macrophage-like THP-1 cells were cultured in a microplate for 4 d with a differentiation agent, phorbol myristate acetate.…”

Section: In Vitro Experimental System For Anti-inflammatory Food Subsmentioning

confidence: 99%

Interaction between Food Substances and the Intestinal Epithelium

Shimizu

2010

Bioscience, Biotechnology, and Biochemistry

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129

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The small intestine is an organ responsible for nutrient absorption, barrier functions, signal recognition/transduction, and the production of bioactive compounds. These functions are known to be regulated by such factors as hormones and cytokines, but substances contained in the daily diet are also thought to play roles as major modulators of intestinal functions. Intestinal epithelial cells (IECs), which form a monolayer covering the inside surface of the intestinal tract, are particularly important in this modulation, because they directly interact with intestinal contents, including food substances, their digests, and gut microbial components. Using cell-based in vitro assays, we investigated the food-IEC interactions at the cellular and molecular levels, and found that a variety of food substances affected the transporter activity, tight junction permeability, metabolic enzyme expression, immune functions, and so on. Modulation of the intestinal functions by dietary substances is therefore essential to promote health.

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“…Resident intestinal macrophages have reduced expression of CD14 (the LPS coreceptor) (40) and tend to be less susceptible to activation by bacterial products (41). In contrast, monocytes are sensitive to bacterial products, and it has been postulated that it is monocytes recruited into tissues that are responsible for local pathology (36,37). For instance, the permeability characteristics of T84 epithelial cell monolayers are unaffected by coculture with LPS-activated lamina propria mononuclear cells (LPMC) isolated from normal human intestine, whereas LPMC from patients with Crohn's disease and monocytes from healthy individuals and patients with Crohn's disease evoke significant increases in epithelial permeability (50).…”

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confidence: 99%

Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenicE. coliis enhanced by TNF-α

Lewis¹,

Caldwell²,

Phan³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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DM. Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-␣. Am J Physiol Gastrointest Liver Physiol 294: G669-G678, 2008. First published January 10, 2008 doi:10.1152/ajpgi.00382.2007.-A defect in mitochondrial activity contributes to many diseases. We have shown that monolayers of the human colonic T84 epithelial cell line exposed to dinitrophenol (DNP, uncouples oxidative phosphorylation) and nonpathogenic Escherichia coli (E. coli) (strain HB101) display decreased barrier function. Here the impact of DNP on macrophage activity and the effect of TNF-␣, DNP, and E. coli on epithelial permeability were assessed. DNP treatment of the human THP-1 macrophage cell line resulted in reduced ATP synthesis, and, although hyporesponsive to LPS, the metabolically stressed macrophages produced IL-1␤, IL-6, and TNF-␣. Given the role of TNF-␣ in inflammatory bowel disease (IBD) and the association between increased permeability and IBD, recombinant TNF-␣ (10 ng/ml) was added to the DNP (0.1 mM) ϩ E. coli (10 6 colony-forming units), and this resulted in a significantly greater loss of T84 epithelial barrier function than that elicited by DNP ϩ E. coli. This increased epithelial permeability was not due to epithelial death, and the enhanced E. coli translocation was reduced by pharmacological inhibitors of NF-␤ signaling (pyrrolidine dithiocarbamate, NF-␤ essential modifier-binding peptide, BAY 11-7082, and the proteosome inhibitor, MG132). In contrast, the drop in transepithelial electrical resistance was unaffected by the inhibitors of NF-␤. Thus, as an integrative model system, our findings support the induction of a positive feedback loop that can severely impair epithelial barrier function and, as such, could contribute to existing inflammation or trigger relapses in IBD. Thus metabolically stressed epithelia display increased permeability in the presence of viable nonpathogenic E. coli that is exaggerated by TNF-␣ released by activated immune cells, such as macrophages, that retain this ability even if they themselves are experiencing a degree of metabolic stress. permeability; bacterial translocation; NFB; T84 cells; macrophages A NUMBER OF PUTATIVE CAUSATIVE agents/mechanisms have been proposed for the inflammatory bowel diseases (IBDs): genetic predisposition, infection, dysregulated immune reactions, triggers from the commensal flora, and a defect in epithelial permeability (44). Abnormal mitochondria have been observed in epithelial cells in tissues resected from patients with Crohn's disease (28), indicating metabolic stress (i.e., ATP depletion) in these individuals. Similarly, reductions in mitochondria acetoacetyl CoA thiolase have been shown in the epithelium of patients with ulcerative colitis, which would result in reduced ATP synthesis from butyrate, and hence these cells would experience a degree of metabolic stress (36). Metabolic stress can arise as a consequence of infection, ischemia, and inflammation itself (8, 14). Thus we hypothes...

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Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha

Cited by 89 publications

References 47 publications

A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials

A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials

Interaction between Food Substances and the Intestinal Epithelium

Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenicE. coliis enhanced by TNF-α

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