Adenosine in Intestinal Epithelial Barrier Function

Stepanova, Mariya; Aherne, Carol M.

doi:10.3390/cells13050381

Cells

2024

DOI: 10.3390/cells13050381

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Adenosine in Intestinal Epithelial Barrier Function

Mariya Stepanova,

Carol M. Aherne

Abstract: At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a few. Their collaboration creates a resilient barrier. In intestinal disorders, such as inflammatory bowel disease (IBD), barrier function is compromised, which results in rampant inflammation and tissue injury. In response to the destruction, the intestinal epithelium releases adenosine, a small but powerful nucleoside that functions as an ala… Show more

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Cited by 3 publications

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Purinergic agonists increase [Ca²⁺]_i in rat conjunctival goblet cells through ryanodine receptor type 3

Fjaervoll,

Yang

et al. 2024

American Journal of Physiology-Cell Physiology

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ATP and BzATP increase free cytosolic Ca2+ concentration ([Ca2+]i) in conjunctival goblet cells (CGCs) resulting in mucin secretion. The purpose of this study was to investigate the source of the Ca2+i mobilized by ATP and BzATP. First passage cultured rat CGCs were incubated with Fura-2/AM and [Ca2+]i was measured under several conditions with ATP and BzATP stimulation. The following conditions were used: 1) preincubation with the Ca2+ chelator EGTA, 2) preincubation with the SERCA inhibitor thapsigargin (10-6 M) which depletes ER Ca2+ stores, 3) preincubation with phospholipase C (PLC) or protein kinase A (PKA) inhibitor, or 4) preincubation with the voltage-gated calcium channel antagonist nifedipine (10-5 M) and the ryanodine receptor (RyR) antagonist dantrolene (10-5 M). Immunofluorescence microscopy (IF) and RT-qPCR were used to investigate RyR presence in rat and human CGCs. ATP stimulated peak [Ca2+]i was significantly lower after chelating Ca2+i with 2 mM EGTA in Ca2+-free buffer. The peak [Ca2+]i increase in CGCs preincubated with thapsigargin, PKA inhibitor H89, nifedipine and dantrolene, but not the PLC inhibitor, was reduced for ATP at 10-5 M and BzATP at 10-4 M. Incubating CGCs with dantrolene alone decreased [Ca2+]i, and induced CGC cell death at a high concentration. RyR3 was detected in rat and human CGCs with IF and RT-qPCR. We conclude that ATP and BzATP-induced Ca2+i increases originate from the ER, and that RyR3 may be an essential regulator of CGC [Ca2+]i. This study contributes to the understanding of diseases arising from defective Ca2+ signaling in non-excitable cells.

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Purinergic agonists increase [Ca²⁺]_i in rat conjunctival goblet cells through ryanodine receptor type 3

Fjaervoll,

Yang

et al. 2024

American Journal of Physiology-Cell Physiology

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Human gut microbiota–reactive DP8α Tregs prevent acute graft-versus-host disease in a CD73-dependent manner

Godefroy,

Chevallier,

Haspot

et al. 2024

JCI Insight

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Graft-versus-host disease (GvHD) is a life-threatening complication frequently occurring following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since gut microbiota and regulatory T cells (Tregs) are believed to play roles in GvHD prevention, we investigated whether DP8a Tregs, which we have previously described to harbor a TCR-specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking microbiota and its effect on GvHD. We observed a decrease in CD73 + DP8a Treg frequency in allo-HSCT patients at 1-month post-transplantation, which was associated with aGvHD development at 1-month post-transplantation, as compared to aGvHD-free patients, without being correlated to hematological disease's relapse. Importantly, CD73 activity was shown to be critical for DP8a Treg suppressive function. Moreover, the frequency of host-reactive DP8aTregs was also lower in aGvHD patients, as compared to aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of these cell subset in GvHD-free patients. We also showed that human DP8a Tregs protected mice against xeno-GvHD through limiting deleterious inflammation and preserving gut integrity. Altogether, these results demonstrated that human DP8a Tregs mediate aGvHD prevention in a CD73dependent manner, likely through host-reactivity, advocating for the use of these cells for the development of innovative therapeutic strategies to preclude aGvHD-related inflammation.

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The Use of Polysaccharide AOP30 from the Rhizome of Alpinia officinarum Hance to Alleviate Lipopolysaccharide-Induced Intestinal Epithelial Barrier Dysfunction and Inflammation via the TLR4/NfκB Signaling Pathway in Caco-2 Cell Monolayers

Jia,

Huang,

Liu

et al. 2024

Nutrients

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Alpinia officinarum Hance is rich in carbohydrates and is flavored by natives. The polysaccharide fraction 30 is purified from the rhizome of A. officinarum Hance (AOP30) and shows excellent immunoregulatory ability when administered to regulate immunity. However, the effect of AOP30 on the intestinal epithelial barrier is not well understood. Therefore, the aim of this study is to investigate the protective effect of AOP30 on the intestinal epithelial barrier using a lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction model and further explore its underlying mechanisms. Cytotoxicity, transepithelial electrical resistance (TEER) values, and Fluorescein isothiocyanate (FITC)–dextran flux are measured. Simultaneously, the protein and mRNA levels of tight junction (TJ) proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1, are determined using Western blotting and reverse-transcription quantitative polymerase chain reaction methods, respectively. The results indicate that AOP30 restores the LPS-induced decrease in the TEER value and cell viability. Furthermore, it increases the mRNA and protein expression of ZO-1, Occludin, and Claudin-1. Notably, ZO-1 is the primary tight junction protein altered in response to LPS-induced intestinal epithelial dysfunction. Additionally, AOP30 downregulates the production of TNFα via the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Collectively, the findings of this study indicate that AOP30 can be developed as a functional food ingredient or natural therapeutic agent for addressing intestinal epithelial barrier dysfunction. It sheds light on the role of AOP30 in improving intestinal epithelial function.

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Adenosine in Intestinal Epithelial Barrier Function

Cited by 3 publications

References 203 publications

Purinergic agonists increase [Ca²⁺]_i in rat conjunctival goblet cells through ryanodine receptor type 3

Purinergic agonists increase [Ca²⁺]_i in rat conjunctival goblet cells through ryanodine receptor type 3

Human gut microbiota–reactive DP8α Tregs prevent acute graft-versus-host disease in a CD73-dependent manner

The Use of Polysaccharide AOP30 from the Rhizome of Alpinia officinarum Hance to Alleviate Lipopolysaccharide-Induced Intestinal Epithelial Barrier Dysfunction and Inflammation via the TLR4/NfκB Signaling Pathway in Caco-2 Cell Monolayers

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Adenosine in Intestinal Epithelial Barrier Function

Cited by 3 publications

References 203 publications

Purinergic agonists increase [Ca2+]i in rat conjunctival goblet cells through ryanodine receptor type 3

Purinergic agonists increase [Ca2+]i in rat conjunctival goblet cells through ryanodine receptor type 3

Human gut microbiota–reactive DP8α Tregs prevent acute graft-versus-host disease in a CD73-dependent manner

The Use of Polysaccharide AOP30 from the Rhizome of Alpinia officinarum Hance to Alleviate Lipopolysaccharide-Induced Intestinal Epithelial Barrier Dysfunction and Inflammation via the TLR4/NfκB Signaling Pathway in Caco-2 Cell Monolayers

Contact Info

Product

Resources

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Purinergic agonists increase [Ca²⁺]_i in rat conjunctival goblet cells through ryanodine receptor type 3

Purinergic agonists increase [Ca²⁺]_i in rat conjunctival goblet cells through ryanodine receptor type 3