scholarly journals Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells

2011 ◽  
Vol 22 (17) ◽  
pp. 3010-3021 ◽  
Author(s):  
Rebecca A. Bozym ◽  
Kunal Patel ◽  
Carl White ◽  
King-Ho Cheung ◽  
Jeffrey M. Bergelson ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Entry ◽  
Calcium Release ◽  
Cell Types ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Viral Pathogens ◽  
Coxsackievirus B ◽  
Calpain 2 ◽  
Trisphosphate Receptor

Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB to promote viral entry and subsequent egress. Here we show that, in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor–dependent calcium release. We further show that CVB-induced cellular necrosis depends on the Ca2+-activated protease calpain-2 and that this protease is involved in CVB-induced disruption of the junctional complex and rearrangements of the actin cytoskeleton. Our study illustrates the cell signaling pathways hijacked by CVB, and perhaps other viral pathogens, to promote their replication and spread in polarized cell types.

scholarly journals RNA regulons are essential in intestinal homeostasis

2019 ◽  
Vol 316 (1) ◽  
pp. G197-G204 ◽  
Author(s):  
Louis R. Parham ◽  
Patrick A. Williams ◽  
Priya Chatterji ◽  
Kelly A. Whelan ◽  
Kathryn E. Hamilton
Keyword(s):  
Epithelial Cells ◽  
Rna Binding ◽  
Environmental Changes ◽  
Cell Function ◽  
Rna Binding Proteins ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
Cell Dynamics ◽  
Functional Roles ◽  
Proliferating Cell

Intestinal epithelial cells are among the most rapidly proliferating cell types in the human body. There are several different subtypes of epithelial cells, each with unique functional roles in responding to the ever-changing environment. The epithelium’s ability for rapid and customized responses to environmental changes requires multitiered levels of gene regulation. An emerging paradigm in gastrointestinal epithelial cells is the regulation of functionally related mRNA families, or regulons, via RNA-binding proteins (RBPs). RBPs represent a rapid and efficient mechanism to regulate gene expression and cell function. In this review, we will provide an overview of intestinal epithelial RBPs and how they contribute specifically to intestinal epithelial stem cell dynamics. In addition, we will highlight key gaps in knowledge in the global understanding of RBPs in gastrointestinal physiology as an opportunity for future studies.

scholarly journals Preventing SARS-CoV-2 infection by blocking a tissue serine protease

2020 ◽  
Vol 7 ◽  
pp. 204993612093307
Author(s):  
Katherine C. Jankousky ◽  
Jonathan Schultz ◽  
Samuel Windham ◽  
Andrés F. Henao-Martínez ◽  
Carlos Franco-Paredes ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Serine Protease ◽  
Viral Entry ◽  
Clinical Impact ◽  
Spike Protein ◽  
Viral Pathogens ◽  
Pharmacological Targets ◽  
Alternative Approach ◽  
Viral Surface

Currently, there are no proven pharmacologic interventions to reduce the clinical impact and prevent complications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the cause of the ongoing Coronavirus Disease of 2019 (COVID-19) pandemic. Selecting specific pharmacological targets for the treatment of viral pathogens has traditionally relied in blockage of specific steps in their replicative lifecycle in human cells. However, an alternative approach is reducing the molecular cleavage of the viral surface spike protein of SARS-CoV-2 to prevent viral entry into epithelial cells.

scholarly journals The Dual Tropism of Noroviruses

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Christiane E. Wobus
Keyword(s):  
Epithelial Cells ◽  
Rna Viruses ◽  
Intestinal Epithelial Cells ◽  
Mammalian Species ◽  
Cell Types ◽  
Economic Losses ◽  
Cell Tropism ◽  
Intestinal Epithelial ◽  
Complex Cell ◽  
Significant Morbidity

ABSTRACTNoroviruses are highly prevalent enteric RNA viruses. Human noroviruses (HuNoVs) cause significant morbidity, mortality, and economic losses worldwide. Infections also occur in other mammalian species, including mice. Despite the discovery of the first norovirus in 1972, the viral tropism has long remained an enigma. A long-held assumption was that these viruses infect intestinal epithelial cells. Recent data support a more complex cell tropism of epithelial and nonepithelial cell types.

scholarly journals Regulation of Inositol 1,4,5-Trisphosphate Receptor-mediated Calcium Release by the Na/K-ATPase in Cultured Renal Epithelial Cells

2007 ◽  
Vol 283 (2) ◽  
pp. 1128-1136 ◽  
Author(s):  
Ying Chen ◽  
Ting Cai ◽  
Changjun Yang ◽  
David A. Turner ◽  
David R. Giovannucci ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Calcium Release ◽  
Renal Epithelial Cells ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

scholarly journals Salmonella entericaserovar Typhimurium regulates intercellular junction proteins and facilitates transepithelial neutrophil and bacterial passage

2007 ◽  
Vol 293 (1) ◽  
pp. G178-G187 ◽  
Author(s):  
Henrik Köhler ◽  
Takanori Sakaguchi ◽  
Bryan P. Hurley ◽  
Benjamin J. Kase ◽  
Hans-Christian Reinecker ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Translocation ◽  
Intestinal Epithelium ◽  
Intestinal Barrier ◽  
Fold Increase ◽  
Molecular Composition ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Serovar Typhimurium ◽  
Triton X

The establishment of tight junctions (TJ) between columnar epithelial cells defines the functional barrier, which enteroinvasive pathogens have to overcome. Salmonella enterica serovar Typhimurium ( S. typhimurium) directly invades intestinal epithelial cells but it is not well understood how the pathogen is able to overcome the intestinal barrier and gains access to the circulation. Therefore, we sought to determine whether infection with S. typhimurium could regulate the molecular composition of the TJ and, if so, whether these modifications would influence bacterial translocation and polymorphonuclear leukocyte (PMN) movement across model intestinal epithelium. We found that infection of a model intestinal epithelium with S. typhimurium over 2 h resulted in an ∼80% loss of transepithelial electrical resistance. Western blot analysis of epithelial cell lysates demonstrated that S. typhimurium regulated the distribution of the TJ complex proteins claudin-1, zonula occludens (ZO)-2, and E-cadherin in Triton X-100-soluble and insoluble fractions. In addition, S. typhimurium was specifically able to dephosphorylate occludin and degrade ZO-1. This TJ alteration in the epithelial monolayer resulted in 10-fold increase in bacterial translocation and a 75% increase in N-formylmethionin-leucyl-phenyalanine-induced PMN transepithelial migration. Our data demonstrate that infection with S. typhimurium is associated with the rapid targeting of the tight junctional complex and loss of barrier function. This results in enhanced bacterial translocation and initiation of PMN migration across the intestinal barrier. Therefore, the ability to regulate the molecular composition of TJs facilitates the pathogenicity of S. typhimurium by aiding its uptake and distribution within the host.

scholarly journals Conjunctival epithelial cells resist productive SARS-CoV-2 infection

2021 ◽  
Author(s):  
Majlinda Lako ◽  
Robert M Jackson ◽  
Catherine F Hatton ◽  
Jarmila S Spegarova ◽  
Maria Georgiou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Entry ◽  
Ocular Surface ◽  
Cell Types ◽  
Productive Infection ◽  
Conjunctival Epithelium ◽  
Genome Expression ◽  
Open Question ◽  
Air Liquid Interface ◽  
Conjunctival Epithelial Cells

Although tropism of SARS-CoV-2 for respiratory tract epithelial cells is well established, an open question is whether the conjunctival epithelium is also a target for SARS-CoV-2. Conjunctival epithelial cells, which express viral entry receptors ACE2 and TMPRSS2, constitute the largest exposed epithelium of the ocular surface tissue, and may represent a relevant viral entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of progenitor, basal and superficial epithelial cells and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA Seq, with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to SARS-CoV-2 genome expression, a productive infection did not ensue. The early innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust autocrine and paracrine NF-Kβ activity, without activation of antiviral interferon signalling. Collectively, these data enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications for the design of preventive strategies and conjunctival transplants.

scholarly journals IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition

2020 ◽  
Author(s):  
Caterina Prelli Bozzo ◽  
Rayhane Nchioua ◽  
Meta Volcic ◽  
Jana Krüger ◽  
Sandra Heller ◽  
...  
Keyword(s):  
Viral Entry ◽  
Human Lung ◽  
Transmembrane Proteins ◽  
Cell Types ◽  
Lung Cells ◽  
Therapeutic Approaches ◽  
Viral Pathogens ◽  
Virus Inhibition ◽  
Human Lung Cells

Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) are thought to restrict numerous viral pathogens including severe acute respiratory syndrome coronaviruses (SARS-CoVs). However, most evidence comes from single-round pseudovirus infection studies of cells that overexpress IFITMs. Here, we verified that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. Strikingly, however, endogenous IFITM expression was essential for efficient infection of genuine SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral entry. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. Intriguingly, IFITM-derived peptides and targeting antibodies inhibited SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are important cofactors for SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and suitable targets for therapeutic approaches.

scholarly journals alpha-Actinin localization in the junctional complex of intestinal epithelial cells.

1979 ◽  
Vol 80 (1) ◽  
pp. 203-210 ◽  
Author(s):  
S W Craig ◽  
J V Pardo
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Sodium Dodecyl ◽  
Junctional Complex ◽  
Intestinal Epithelial ◽  
Membrane Structures ◽  
Apical Portion ◽  
Chicken Gizzard ◽  
Subunit Molecular Weight ◽  
Polygonal Pattern

We have used antibody to chicken gizzard alpha-actinin to identify and localize this molecule in chicken intestinal epithelium. The antibody binds only to alpha-actinin when tested against a crude extract of chicken gizzard. Extracts of purified epithelial cells contain a molecule which has a subunit molecular weight of 100,000 on sodium dodecyl sulphate gels and which is able to inhibit the interaction of alpha-actinin antibody and 125I-labeled chicken gizzard alpha-actinin. By indirect immunofluorescence, alpha-actinin is localized in the apical portion of chicken intestinal epithelial cells. Ethanol-fixed cryostat sections of intestine taken through the apical portion of the epithelial cells and in a plane perpendicular to the long axis of the cells show that alpha-actinin is organized in a polygonal pattern which corresponds to the outlines of the polygonally packed epithelial cells. We interpret the data as indicating that alpha-actinin is a component of the tight junction (zonula occludens) and/or the belt desmosome (zonula adherens), both of which are membrane structures known to encircle the cell and to be confined to its apical portion.

scholarly journals Immunomodulatory Effects of TGF-β Family Signaling within Intestinal Epithelial Cells and Carcinomas

2019 ◽  
Vol 1 (2) ◽  
pp. 290-300
Author(s):  
Paula Marincola Smith ◽  
Anna Means ◽  
R. Beauchamp
Keyword(s):  
Epithelial Cells ◽  
Cytokine Production ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Immunomodulatory Effects ◽  
Cellular Functions ◽  
Epithelial Cancers ◽  
Causal Pathways

TGF-β superfamily signaling is responsible for many critical cellular functions including control of cell growth, cell proliferation, cell differentiation, and apoptosis. TGF-β appears to be critical in gastrulation, embryonic development, and morphogenesis, and it retains pleiotropic roles in many adult tissues and cell types in a highly context-dependent manner. While TGF-β signaling within leukocytes is known to have an immunosuppressive role, its immunomodulatory effects within epithelial cells and epithelial cancers is less well understood. Recent data has emerged that suggests TGF-β pathway signaling within epithelial cells may directly modulate pro-inflammatory chemokine/cytokine production and resultant leukocyte recruitment. This immunomodulation by epithelial TGF-β pathway signaling may directly impact tumorigenesis and tumor progression through modulation of the epithelial microenvironment, although causal pathways responsible for such an observation remain incompletely investigated. This review presents the published literature as it relates to the immunomodulatory effects of TGF-β family signaling within intestinal epithelial cells and carcinomas.

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