-
Frontiers in Immunology 2020Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research... (Review)
Review
Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research have elucidated host mechanisms that contribute to the bacterial clearance where an indispensable role of immune cells has been established. However, the role of respiratory epithelial cells in bacterial clearance has garnered limited attention due to their weak inflammatory or phagocytic ability compared to immune cells such as macrophages and neutrophils. These studies often underappreciate the fact that epithelial cells are the most abundant cells in the lung, not only serving as building blocks but also providing immune protection throughout the lung. Epithelial cells function either independently to eradicate the pathogen or communicate with immune cells to orchestrate pathogen clearance. The epithelial cells have multiple mechanisms that include mucus production, antimicrobial peptide production, muco-ciliary clearance, and phagocytosis, all of which contribute to their direct antibacterial function. Secretion of cytokines to recruit immune cells and potentiate their antimicrobial activities is a pathway by which the epithelium contributes to bacterial clearance. Successful pathogens outsmart epithelial resistance and find a way to replicate in sufficient numbers to establish infections in the airway or lung epithelial surfaces. In this mini-review, we discuss evidences that establish important roles for epithelial host defense against invading respiratory bacterial pathogens and demonstrate how pathogens outsmart these epithelial immune mechanisms to successfully establish infection. Finally, we discuss briefly how to boost epithelial immunity to improve outcomes in bacterial lung infections.
Topics: Animals; Bacteria; Bacterial Infections; Cytokines; Epithelial Cells; Humans; Immune Evasion; Lung; Macrophages; Neutrophils; Phagocytosis; Respiratory Mucosa; Respiratory Tract Infections
PubMed: 32117248
DOI: 10.3389/fimmu.2020.00091 -
Cells, Tissues, Organs 2022The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity... (Review)
Review
The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.
Topics: Epithelial-Mesenchymal Transition; Humans; Neoplasms
PubMed: 33902034
DOI: 10.1159/000515289 -
Cell Research May 2012The polarized distribution of proteins and lipids at the surface membrane of epithelial cells results in the formation of an apical and a basolateral domain, which are... (Review)
Review
The polarized distribution of proteins and lipids at the surface membrane of epithelial cells results in the formation of an apical and a basolateral domain, which are separated by tight junctions. The generation and maintenance of epithelial polarity require elaborate mechanisms that guarantee correct sorting and vectorial delivery of cargo molecules. This dynamic process involves the interaction of sorting signals with sorting machineries and the formation of transport carriers. Here we review the recent advances in the field of polarized sorting in epithelial cells. We especially highlight the role of lipid rafts in apical sorting.
Topics: Animals; Biological Transport; Cell Polarity; Cell Tracking; Epithelial Cells; Humans; Membrane Lipids; Membrane Microdomains; Membrane Proteins
PubMed: 22525333
DOI: 10.1038/cr.2012.64 -
Toxicology and Applied Pharmacology Apr 2018Epidemiological and experimental studies have implicated cadmium (Cd) with breast cancer. In breast epithelial MCF10A and MDA-MB-231 cells, Cd has been shown to promote...
Epidemiological and experimental studies have implicated cadmium (Cd) with breast cancer. In breast epithelial MCF10A and MDA-MB-231 cells, Cd has been shown to promote cell growth. The present study examined whether Cd also promotes epithelial-mesenchymal transition (EMT), a hallmark of cancer progression. Human breast epithelial cells consisting of non-cancerous MCF10A, non-metastatic HCC 1937 and HCC 38, and metastatic MDA-MB-231 were treated with 1 or 3 μM Cd for 4 weeks. The MCF10A epithelial cells switched to a more mesenchymal-like morphology, which was accompanied by a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal markers N-cadherin and vimentin. In both non-metastatic HCC 1937 and HCC 38 cells, treatment with Cd decreased the epithelial marker claudin-1. In addition, E-cadherin also decreased in the HCC 1937 cells. Even the mesenchymal-like MDA-MB-231 cells exhibited an increase in the mesenchymal marker vimentin. These changes indicated that prolonged treatment with Cd resulted in EMT in both normal and cancer-derived breast epithelial cells. Furthermore, both the MCF10A and MDA-MB-231 cells labeled with Zcad, a dual sensor for tracking EMT, demonstrated a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker ZEB-1. Treatment of cells with Cd significantly increased the level of Snail, a transcription factor involved in the regulation of EMT. However, the Cd-induced Snail expression was completely abolished by actinomycin D. Luciferase reporter assay indicated that the expression of Snail was regulated by Cd at the promotor level. Snail was essential for Cd-induced promotion of EMT in the MDA-MB-231 cells, as knockdown of Snail expression blocked Cd-induced cell migration. Together, these results indicate that Cd promotes EMT in breast epithelial cells and does so by modulating the transcription of Snail.
Topics: Antigens, CD; Breast; Cadherins; Cadmium; Dose-Response Relationship, Drug; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Snail Family Transcription Factors
PubMed: 29501589
DOI: 10.1016/j.taap.2018.02.022 -
Chinese Journal of Cancer Nov 2014Epstein-Barr virus (EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma (NPC), strongly implicating a role for EBV in NPC pathogenesis;... (Review)
Review
Epstein-Barr virus (EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma (NPC), strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in normal nasopharyngeal epithelial tissues. In general, EBV does not show a strong tropism for infecting human epithelial cells, and EBV infection in oropharyngeal epithelial cells is believed to be lytic in nature. To establish life-long infection in humans, EBV has evolved efficient strategies to infect B cells and hijack their cellular machinery for latent infection. Lytic EBV infection in oropharyngeal epithelial cells, though an infrequent event, is believed to be a major source of infectious EBV particles for salivary transmission. The biological events associated with nasopharyngeal epithelial cells are only beginning to be understood with the advancement of EBV infection methods and the availability of nasopharyngeal epithelial cell models for EBV infection studies. EBV infection in human epithelial cells is a highly inefficient process compared to that in B cells, which express the complement receptor type 2 (CR2) to mediate EBV infection. Although receptor(s) on the epithelial cell surface for EBV infection remain(s) to be identified, EBV infection in epithelial cells could be achieved via the interaction of glycoproteins on the viral envelope with surface integrins on epithelial cells, which might trigger membrane fusion to internalize EBV in cells. Normal nasopharyngeal epithelial cells are not permissive for latent EBV infection, and EBV infection in normal nasopharyngeal epithelial cells usually results in growth arrest. However, genetic alterations in premalignant nasopharyngeal epithelial cells, including p16 deletion and cyclin D1 overexpression, could override the growth inhibitory effect of EBV infection to support stable and latent EBV infection in nasopharyngeal epithelial cells. The EBV episome in NPC is clonal in nature, suggesting that NPC develops from a single EBV-infected nasopharyngeal epithelial cell, and the establishment of persistent and latent EBV infection in premalignant nasopharyngeal epithelium may represent an early and critical event for NPC development.
Topics: Carcinoma; Cell Transformation, Neoplastic; Cells, Cultured; Epithelial Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Precancerous Conditions
PubMed: 25223910
DOI: 10.5732/cjc.014.10169 -
Taiwanese Journal of Obstetrics &... Sep 2021
Topics: Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms
PubMed: 34507651
DOI: 10.1016/j.tjog.2021.07.003 -
Annals of the New York Academy of... Oct 2017Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and... (Review)
Review
Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and basolateral membrane domains separated by intercellular junctions, including tight junctions (TJs), which contribute to the maintenance of apical-basal polarity. Polarity complexes also contribute to the establishment of TJ formation. Several pathogens perturb epithelial TJ barrier function and structure in addition to causing a loss of apical-basal polarity. Here, we review the impact of pathogenic bacteria on the disruption of cell-cell junctions and epithelial polarity.
Topics: Animals; Cell Polarity; Epithelial Cells; Escherichia coli; Humans; Membrane Proteins; Tight Junctions
PubMed: 28628193
DOI: 10.1111/nyas.13388 -
Mediators of Inflammation 2015In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate... (Review)
Review
In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed.
Topics: Animals; Bronchi; Cystic Fibrosis Transmembrane Conductance Regulator; Cytokines; Epithelial Cells; Epithelial Sodium Channels; Humans; Immunity, Innate; Ion Channels
PubMed: 26185361
DOI: 10.1155/2015/463016 -
Stem Cells and Development Jan 2010Recent advances in the biology of stem cells has resulted in significant interest in the development of normal epithelial cell lines from the intestinal mucosa, both to... (Review)
Review
Recent advances in the biology of stem cells has resulted in significant interest in the development of normal epithelial cell lines from the intestinal mucosa, both to exploit the therapeutic potential of stem cells in tissue regeneration and to develop treatment models of degenerative disorders of the digestive tract. However, the difficulty of propagating cell lines of normal intestinal epithelium has impeded research into the molecular mechanisms underlying differentiation of stem/progenitor cells into the various intestinal lineages. Several short-term organ/organoid and epithelial cell culture models have been described. There is a dearth of long-term epithelial and/or stem cell cultures of intestine. With an expanding role of stem cells in the treatment of degenerative disorders, there is a critical need for additional efforts to develop in vitro models of stem/progenitor epithelial cells of intestine. The objective of this review is to recapitulate the current status of technologies and knowledge for in vitro propagation of intestinal epithelial cells, markers of the intestinal stem cells, and gene and protein expression profiles of the intestinal cellular differentiation.
Topics: Algorithms; Animals; Cell Differentiation; Cells, Cultured; Epithelial Cells; Gene Expression Profiling; Humans; Intestinal Mucosa; Models, Biological; Organ Culture Techniques; Tissue Engineering
PubMed: 19580443
DOI: 10.1089/scd.2009.0109 -
Developmental Cell Jun 2023Mesenchymal-epithelial transitions are fundamental drivers of development and disease, but how these behaviors generate epithelial structure is not well understood....
Mesenchymal-epithelial transitions are fundamental drivers of development and disease, but how these behaviors generate epithelial structure is not well understood. Here, we show that mesenchymal-epithelial transitions promote epithelial organization in the mouse node and notochordal plate through the assembly and radial intercalation of three-dimensional rosettes. Axial mesoderm rosettes acquire junctional and apical polarity, develop a central lumen, and dynamically expand, coalesce, and radially intercalate into the surface epithelium, converting mesenchymal-epithelial transitions into higher-order tissue structure. In mouse Par3 mutants, axial mesoderm rosettes establish central tight junction polarity but fail to form an expanded apical domain and lumen. These defects are associated with altered rosette dynamics, delayed radial intercalation, and formation of a small, fragmented surface epithelial structure. These results demonstrate that three-dimensional rosette behaviors translate mesenchymal-epithelial transitions into collective radial intercalation and epithelial formation, providing a strategy for building epithelial sheets from individual self-organizing units in the mammalian embryo.
Topics: Animals; Mice; Mesoderm; Epithelium; Cell Differentiation; Embryo, Mammalian; Morphogenesis; Mammals
PubMed: 37080203
DOI: 10.1016/j.devcel.2023.03.018