scholarly journals Interplay Between Microbiota, Toll-Like Receptors and Cytokines for the Maintenance of Epithelial Barrier Integrity

2021 ◽  
Vol 8 ◽  
Author(s):  
Iaroslav Semin ◽  
Justus Ninnemann ◽  
Marina Bondareva ◽  
Ilia Gimaev ◽  
Andrey A. Kruglov
Keyword(s):  
Epithelial Cells ◽  
Single Layer ◽  
Living Organism ◽  
The Body ◽  
Epithelial Barrier ◽  
Epithelial Tissue ◽  
Toll Like Receptors ◽  
Tissue Integrity ◽  
Healthy State

The intestinal tract is densely populated by microbiota consisting of various commensal microorganisms that are instrumental for the healthy state of the living organism. Such commensals generate various molecules that can be recognized by the Toll-like receptors of the immune system leading to the inflammation marked by strong upregulation of various proinflammatory cytokines, such as TNF, IL-6, and IL-1β. To prevent excessive inflammation, a single layer of constantly renewing, highly proliferating epithelial cells (IEC) provides proper segregation of such microorganisms from the body cavities. There are various triggers which facilitate the disturbance of the epithelial barrier which often leads to inflammation. However, the nature and duration of the stress may determine the state of the epithelial cells and their responses to cytokines. Here we discuss the role of the microbiota-TLR-cytokine axis in the maintenance of the epithelial tissue integrity. In particular, we highlight discrepancies in the function of TLR and cytokines in IEC barrier during acute or chronic inflammation and we suggest that intervention strategies should be applied based on the type of inflammation.

scholarly journals Role of toll-like receptors in human iris pigment epithelial cells and their response to pathogen-associated molecular patterns

2014 ◽  
Vol 11 (1) ◽  
pp. 20 ◽  
Author(s):  
Kelly Mai ◽  
Jeanie JY Chui ◽  
Nick Di Girolamo ◽  
Peter J McCluskey ◽  
Denis Wakefield
Keyword(s):  
Epithelial Cells ◽  
Toll Like Receptors ◽  
Pigment Epithelial ◽  
Human Iris ◽  
Molecular Patterns ◽  
Pigment Epithelial Cells

scholarly journals Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3194
Author(s):  
Yutaka Suzuki ◽  
Sachi Chiba ◽  
Koki Nishihara ◽  
Keiichi Nakajima ◽  
Akihiko Hagino ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Dairy Cows ◽  
Barrier Function ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Barrier ◽  
Epithelial Tissue ◽  
Epithelial Barrier Function

Epithelial barrier function in the mammary gland acts as a forefront of the defense mechanism against mastitis, which is widespread and a major disorder in dairy production. Chemerin is a chemoattractant protein with potent antimicrobial ability, but its role in the mammary gland remains unelucidated. The aim of this study was to determine the function of chemerin in mammary epithelial tissue of dairy cows in lactation or dry-off periods. Mammary epithelial cells produced chemerin protein, and secreted chemerin was detected in milk samples. Chemerin treatment promoted the proliferation of cultured bovine mammary epithelial cells and protected the integrity of the epithelial cell layer from hydrogen peroxide (H2O2)-induced damage. Meanwhile, chemerin levels were higher in mammary tissue with mastitis. Tumor necrosis factor alpha (TNF-α) strongly upregulated the expression of the chemerin-coding gene (RARRES2) in mammary epithelial cells. Therefore, chemerin was suggested to support mammary epithelial cell growth and epithelial barrier function and to be regulated by inflammatory stimuli. Our results may indicate chemerin as a novel therapeutic target for diseases in the bovine mammary gland.

scholarly journals Porphyromonas gingivalis Impairs Oral Epithelial Barrier through Targeting GRHL2

2019 ◽  
Vol 98 (10) ◽  
pp. 1150-1158 ◽  
Author(s):  
W. Chen ◽  
A. Alshaikh ◽  
S. Kim ◽  
J. Kim ◽  
C. Chun ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Oral Mucosa ◽  
Porphyromonas Gingivalis ◽  
Oral Bacteria ◽  
Conditional Knockout ◽  
Epithelial Barrier ◽  
Wild Type ◽  
Oral Epithelial ◽  
Junction Proteins

Oral mucosa provides the first line of defense against a diverse array of environmental and microbial irritants by forming the barrier of epithelial cells interconnected by multiprotein tight junctions (TJ), adherens junctions, desmosomes, and gap junction complexes. Grainyhead-like 2 (GRHL2), an epithelial-specific transcription factor, may play a role in the formation of the mucosal epithelial barrier, as it regulates the expression of the junction proteins. The current study investigated the role of GRHL2 in the Porphyromonas gingivalis ( Pg)–induced impairment of epithelial barrier functions. Exposure of human oral keratinocytes (HOK-16B and OKF6 cells) to Pg or Pg-derived lipopolysaccharides ( Pg LPSs) led to rapid loss of endogenous GRHL2 and the junction proteins (e.g., zonula occludens, E-cadherin, claudins, and occludin). GRHL2 directly regulated the expression levels of the junction proteins and the epithelial permeability for small molecules (e.g., dextrans and Pg bacteria). To explore the functional role of GRHL2 in oral mucosal barrier, we used a Grhl2 conditional knockout (KO) mouse model, which allows for epithelial tissue-specific Grhl2 KO in an inducible manner. Grhl2 KO impaired the expression of the junction proteins at the junctional epithelium and increased the alveolar bone loss in the ligature-induced periodontitis model. Fluorescence in situ hybridization revealed increased epithelial penetration of oral bacteria in Grhl2 KO mice compared with the wild-type mice. Also, blood loadings of oral bacteria (e.g., Bacteroides, Bacillus, Firmicutes, β- proteobacteria, and Spirochetes) were significantly elevated in Grhl2 KO mice compared to the wild-type littermates. These data indicate that Pg bacteria may enhance paracellular penetration through oral mucosa in part by targeting the expression of GRHL2 in the oral epithelial cells, which then impairs the epithelial barrier by inhibition of junction protein expression, resulting in increased alveolar tissue destruction and systemic bacteremia.

scholarly journals Neurons and Glia in the Enteric Nervous System and Epithelial Barrier Function

Physiology ◽  
2018 ◽  
Vol 33 (4) ◽  
pp. 269-280 ◽  
Author(s):  
Nathalie Vergnolle ◽  
Carla Cirillo
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Barrier Function ◽  
Current Knowledge ◽  
The Body ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Barrier Function ◽  
Exchange Surface

The intestinal epithelial barrier is the largest exchange surface between the body and the external environment. Its functions are regulated by luminal, and also internal, components including the enteric nervous system. This review summarizes current knowledge about the role of the digestive “neuronal-glial-epithelial unit” on epithelial barrier function.

scholarly journals Role of Intestinal Epithelial Cells in Immune Effects Mediated by Gram-Positive Probiotic Bacteria: Involvement of Toll-Like Receptors

2005 ◽  
Vol 12 (9) ◽  
pp. 1075-1084 ◽  
Author(s):  
Gabriel Vinderola ◽  
Chantal Matar ◽  
Gabriela Perdigon
Keyword(s):  
Small Intestine ◽  
B Cells ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Primary Cultures ◽  
Clonal Expansion ◽  
Probiotic Bacteria ◽  
Intestinal Epithelial ◽  
Toll Like Receptors

ABSTRACT The mechanisms by which probiotic bacteria exert their effects on the immune system are not completely understood, but the epithelium may be a crucial player in the orchestration of the effects induced. In a previous work, we observed that some orally administered strains of lactic acid bacteria (LAB) increased the number of immunoglobulin A (IgA)-producing cells in the small intestine without a concomitant increase in the CD4+ T-cell population, indicating that some LAB strains induce clonal expansion only of B cells triggered to produce IgA. The present work aimed to study the cytokines induced by the interaction of probiotic LAB with murine intestinal epithelial cells (IEC) in healthy animals. We focused our investigation mainly on the secretion of interleukin 6 (IL-6) necessary for the clonal expansion of B cells previously observed with probiotic bacteria. The role of Toll-like receptors (TLRs) in such interaction was also addressed. The cytokines released by primary cultures of IEC in animals fed with Lactobacillus casei CRL 431 or Lactobacillus helveticus R389 were determined. Cytokines were also determined in the supernatants of primary cultures of IEC of unfed animals challenged with different concentrations of viable or nonviable lactobacilli and Escherichia coli, previously blocked or not with anti-TLR2 and anti-TLR4. We concluded that the small intestine is the place where a major distinction would occur between probiotic LAB and pathogens. This distinction comprises the type of cytokines released and the magnitude of the response, cutting across the line that separates IL-6 necessary for B-cell differentiation, which was the case with probiotic lactobacilli, from inflammatory levels of IL-6 for pathogens.

scholarly journals Macrophages and Epithelial Cells Mutually Interact through NLRP3 to Clear Infection and Enhance the Gastrointestinal Barrier

Immuno ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 13-25
Author(s):  
Michael Bording-Jorgensen ◽  
Heather Armstrong ◽  
Madison Wickenberg ◽  
Paul LaPointe ◽  
Eytan Wine
Keyword(s):  
Epithelial Cells ◽  
Receptor Protein ◽  
Epithelial Barrier ◽  
Inflammasome Activation ◽  
Colonic Epithelial Cells ◽  
Epithelial Barrier Function ◽  
Barrier Integrity ◽  
Pathogen Control ◽  
Pathogen Clearance

Activation of the nod-like receptor protein 3 (NLRP3) leads to the release of the proinflammatory cytokine IL-1β, which then facilitates pathogen control by macrophages. The role of NLRPs in controlling infection of epithelial cells is not well understood. Our hypothesis was that activation of the NLRP3 inflammasome in colonic epithelial cells would promote macrophage-mediated epithelial recovery after infection with the pathogen Citrobacter rodentium. We devised a co-culture model using mouse colonic epithelial cells (CMT-93) and macrophages (J774A.1) during infection with C. rodentium. Inflammasome was activated using LPS and ATP and inhibited by YVAD. We assessed cytokine secretion (ELISA), macrophage recruitment and pathogen penetration (immunofluorescence), and epithelial barrier integrity (transepithelial electrical resistance). Macrophages were recruited to the apical membrane of epithelial cells, associated with tight junctions, promoted epithelial barrier recovery, and displaced C. rodentium. While NLRP3 was expressed in infected epithelial cells, IL-18 or IL-1β secretion remained unchanged. Supernatants from infected epithelial cells promoted infection clearance by macrophage; while this was inflammasome-independent, ATP significantly improved epithelial barrier recovery. The inflammasome appears to promote epithelial barrier function, independent of IL-18 and IL-1β secretion. Inflammasome activation in macrophages plays a dual role of promoting pathogen clearance and improving epithelial barrier integrity.

scholarly journals Inactivation of the Wnt/β-catenin signaling contributes to the epithelial barrier dysfunction induced by sodium oxalate in canine renal epithelial cells

2021 ◽  
Author(s):  
Yun Ji ◽  
Shuting Fang ◽  
Ying Yang ◽  
Zhenlong Wu
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Mdck Cells ◽  
Renal Stones ◽  
Sodium Oxalate ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Epithelial Barrier Dysfunction

Abstract Background Nephrolithiasis (also known as renal stones) is a common disease condition in companion animals, including dogs and cats. Dysfunction of renal tubular epithelial cells involves in the pathogenesis of renal stones. However, a functional role of Wnt/β-catenin signaling and its contribution to nephrolithiasis remains unknown. Results In the present study, we found that Mardin-Darby canine kidney (MDCK) cells treated with sodium oxalate resulted in reduced cell proliferation and migration, which was associated with the G0/G1 phase arrest of cell cycle progression. In addition, sodium oxalate exposure led to decreased transepithelial electrical resistance (TEER) and increased paracellular permeability. The deleterious effect of sodium oxalate on epithelial barrier function was related to decreased protein abundances of claudin-1, occludin, zonula occludens (ZO)-1, ZO-2 and ZO-3. Of note, protein levels of p-β-catenin (Ser552) in MDCK cells were repressed by sodium oxalate, indicating an inhibitory effect on the Wnt/β-catenin signaling. Intriguingly, SB216763, a GSK-3β inhibitor, enhanced the expression p-β-catenin (Ser552), and protected against epithelial barrier dysfunction in sodium oxalate-treated MDCK cells. Conclusion Taken together, our results revealed a critical role of Wnt/β-catenin signaling on the epithelial barrier function of MDCK cells. Activation of Wnt/β-catenin signaling might be an potentially therapeutic target for the treatment of renal stones in animals.

scholarly journals MODERN VIEWS ON ROLE OF VITAMIN D IN PATHOGENESIS OF BRONCHIAL ASTHMA IN CHILDREN

2020 ◽  
Vol 8 (4) ◽  
pp. 617-628
Author(s):  
N.A. Belykh ◽  
◽  
I.V. Piznyur ◽  
Keyword(s):  
Vitamin D ◽  
Epithelial Cells ◽  
Bronchial Asthma ◽  
Airway Remodeling ◽  
Current Trend ◽  
Tissue Growth ◽  
The Body ◽  
Common Disease ◽  
Mesenchymal Transition

Bronchial asthma (BA) is a common disease of airways in children characterized by chronic inflammation, as well as respiratory symptoms varying in time and intensity. In recent years, an increase in the prevalence of BA has been seen, both among the adult and children’s population. The current trend stimulates scientists to continue studying the probable influence of various factors on this process, including the role of micronutrient deficiency, especially antioxidants, methylene donors and vitamin D (VD). Hypovitaminosis D has been considered as a provoking factor affecting the pathogenesis of various pathological processes. The results of numerous studies confirm the opinion that VD affects the intensity of inflammation, reducing the produc-tion of proinflammatory cytokines and secretion of mucus, and stimulates the secretion of the antiinflammatory cytokine IL-10. VD-regulated genes encode the synthesis of antimicrobial peptides that provide protection against bacteria and viruses provoking BA exacerbations. The article discusses the role of tissue growth factor (TGF-β) as an initiator of fibrosis in the epithelial cells of the respiratory tract through the activation of epithelial mesenchymal transition signals, and also discusses the inhibitory effect of VD on the processes of airway remodeling in BA. To-day it is known that VD can inhibit the progression of pulmonary fibrosis in various ways, in-cluding suppression of the expression of TGF, inhibition of the motility of epithelial cells induced by TGF-β, reduction of the excessive activation of RAS (antifibrotic effect), increase in the level of TGF antagonist. Separately, the issue of the possible strengthening of the antioxidant defense of the body in BA is considered through optimization of the supply of the organism with VD. Conclusion. Thus, taking into account the fact that to date, the results of clinical studies of the use of VD in the treatment of BA gave conflicting results, additional studies are needed to address controversial issues regarding the role of VD deficiency in the pathogenesis of BA and its control. Further understanding of the mechanisms underlying the airway remodeling will help develop a set of measures aimed at minimizing the risk of structural changes in AD.

scholarly journals Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 4-23
Author(s):  
A. V. Gaponova ◽  
S. Rodin ◽  
A. A. Mazina ◽  
P. V. Volchkov
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Tumor Dissemination

About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

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