Polyunsaturated Fatty Acid-Derived Lipid Mediators That Regulate Epithelial Homeostasis

Naganuma, Tatsuro; Fujinami, Nodoka; Arita, Makoto

doi:10.1248/bpb.b22-00252

Cited by 4 publications

(3 citation statements)

References 109 publications

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“…Lastly, the arachidonate generation from DAG pathway, responsible for producing bioactive lipid mediators involved in inflammation, indicates that P80 might influence epithelial cell inflammatory responses and immune process regulation within the barrier. 46 In addition, proteome pathway analysis revealed that while P20 treatment elicits a Th1-prone immune response, P80 treatment initiates a Th2-driven response indicative of tissue restoration, cellular senescence due to oxidative stress and potentially decreased ROS scavenging proteins, aligning with prior research on P80's potential to increase oxidative stress susceptibility by reducing glutathione levels. 47 Weighted co-expression network analysis was performed to visualize the overall picture of differentially expressed proteins by identifying the key modifying players (hub proteins) in response to P20 and P80.…”

Section: Discussionsupporting

confidence: 57%

“…Alterations in this pathway due to P80 exposure may impact the barrier's capacity to maintain structural integrity and appropriate cellular interactions. Lastly, the arachidonate generation from DAG pathway, responsible for producing bioactive lipid mediators involved in inflammation, indicates that P80 might influence epithelial cell inflammatory responses and immune process regulation within the barrier 46 . In addition, proteome pathway analysis revealed that while P20 treatment elicits a Th1‐prone immune response, P80 treatment initiates a Th2‐driven response indicative of tissue restoration, cellular senescence due to oxidative stress and potentially decreased ROS scavenging proteins, aligning with prior research on P80's potential to increase oxidative stress susceptibility by reducing glutathione levels 47 …”

Section: Discussionmentioning

confidence: 99%

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Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

Ogulur,

Yazici,

Pat

et al. 2023

Allergy

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BackgroundThe rising prevalence of many chronic diseases related to gut barrier dysfunction coincides with the increased global usage of dietary emulsifiers in recent decades. We therefore investigated the effect of the frequently used food emulsifiers on cytotoxicity, barrier function, transcriptome alterations, and protein expression in gastrointestinal epithelial cells.MethodsHuman intestinal organoids originating from induced pluripotent stem cells, colon organoid organ‐on‐a‐chip, and liquid–liquid interface cells were cultured in the presence of two common emulsifiers: polysorbate 20 (P20) and polysorbate 80 (P80). The cytotoxicity, transepithelial electrical resistance (TEER), and paracellular‐flux were measured. Immunofluorescence staining of epithelial tight‐junctions (TJ), RNA‐seq transcriptome, and targeted proteomics were performed.ResultsCells showed lysis in response to P20 and P80 exposure starting at a 0.1% (v/v) concentration across all models. Epithelial barrier disruption correlated with decreased TEER, increased paracellular‐flux and irregular TJ immunostaining. RNA‐seq and targeted proteomics analyses demonstrated upregulation of cell development, signaling, proliferation, apoptosis, inflammatory response, and response to stress at 0.05%, a concentration lower than direct cell toxicity. A proinflammatory response was characterized by the secretion of several cytokines and chemokines, interaction with their receptors, and PI3K‐Akt and MAPK signaling pathways. CXCL5, CXCL10, and VEGFA were upregulated in response to P20 and CXCL1, CXCL8 (IL‐8), CXCL10, LIF in response to P80.ConclusionsThe present study provides direct evidence on the detrimental effects of food emulsifiers P20 and P80 on intestinal epithelial integrity. The underlying mechanism of epithelial barrier disruption was cell death at concentrations between 1% and 0.1%. Even at concentrations lower than 0.1%, these polysorbates induced a proinflammatory response suggesting a detrimental effect on gastrointestinal health.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

Ogulur,

Yazici,

Pat

et al. 2023

Allergy

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show abstract

“…They may modulate gut microbiota composition and activity, indirectly influencing TC function and inflammation in IBD [ 134 ]. Omega-3 fatty acids, found in fatty fish, flaxseeds, and walnuts, have anti-inflammatory effects and may help reduce inflammation in IBD [ 135 , 136 ]. While their direct effects on TCs are not well studied, their overall impact on gut health may indirectly influence TC function.…”

Section: Tuft-cell-based Ibd Treatment Options and Their Controversiesmentioning

confidence: 99%

Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer

Sipos,

Műzes

2024

IJMS

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Tuft cells are more than guardian chemosensory elements of the digestive tract. They produce a variety of immunological effector molecules in response to stimulation; moreover, they are essential for defense against protozoa and nematodes. Beyond the description of their characteristics, this review aims to elucidate the potential pathogenic and therapeutic roles of colonic tuft cells in inflammatory bowel disease and colorectal cancer, focusing on their primarily immunomodulatory action. Regarding inflammatory bowel disease, tuft cells are implicated in both maintaining the integrity of the intestinal epithelial barrier and in tissue repair and regeneration processes. In addition to maintaining intestinal homeostasis, they display complex immune-regulatory functions. During the development of colorectal cancer, tuft cells can promote the epithelial-to-mesenchymal transition, alter the gastrointestinal microenvironment, and modulate both the anti-tumor immune response and the tumor microenvironment. A wide variety of their biological functions can be targeted for anti-inflammatory or anti-tumor therapies; however, the adverse side effects of immunomodulatory actions must be strictly considered.

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Bioactive lipids in the skin barrier mediate its functionality in health and disease

Nicolaou,

Kendall

2024

Pharmacology & Therapeutics

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Polyunsaturated Fatty Acid-Derived Lipid Mediators That Regulate Epithelial Homeostasis

Cited by 4 publications

References 109 publications

Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer

Bioactive lipids in the skin barrier mediate its functionality in health and disease

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