Academic Journal
View in EDS

Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells Through the Inhibition of Rac1

Bibliographic Details
Title: Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells Through the Inhibition of Rac1
Authors: Gerco den Hartog, Lindsay D. Butcher, Amber L. Ablack, Laura A. Pace, Jailal N. G. Ablack, Richard Xiong, Soumita Das, Thaddeus S. Stappenbeck, Lars Eckmann, Peter B. Ernst, Sheila E. Crowe
Source: Frontiers in Immunology, Vol 11 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: intestinal epithelial barrier, invasion, internalization, Rac1, Salmonella Typhimurium, AIEC LF82 strain, Immunologic diseases. Allergy, RC581-607
More Details: Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected with Salmonella enterica serovar Typhimurium or adherent-invasive Escherichia coli. The effects of APE1 inhibition on bacterial internalization, the regulation of Rho GTPase Rac1 as well as the epithelial cell barrier function were assessed. Increased numbers of bacteria were present in APE1-deficient colonic tumor cell lines and primary epithelial cells. Activation of Rac1 was augmented following infection but negatively regulated by APE1. Pharmacological inhibition of Rac1 reversed the increase in intracellular bacteria in APE1-deficient cells whereas overexpression of constitutively active Rac1 augmented the numbers in APE1-competent cells. Enhanced numbers of intracellular bacteria resulted in the loss of barrier function and a delay in its recovery. Our data demonstrate that APE1 inhibits the internalization of invasive bacteria into human intestinal epithelial cells through its ability to negatively regulate Rac1. This activity also protects epithelial cell barrier function.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2020.553994/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2020.553994
Access URL: https://doaj.org/article/909a51ee968d491cb7336a83d534599b
Accession Number: edsdoj.909a51ee968d491cb7336a83d534599b
Database: Directory of Open Access Journals
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edsdoj&genre=article&issn=16643224&ISBN=&volume=11&issue=&date=20210201&spage=&pages=&title=Frontiers in Immunology&atitle=Apurinic%2FApyrimidinic%20Endonuclease%201%20Restricts%20the%20Internalization%20of%20Bacteria%20Into%20Human%20Intestinal%20Epithelial%20Cells%20Through%20the%20Inhibition%20of%20Rac1&aulast=Gerco%20den%20Hartog&id=DOI:10.3389/fimmu.2020.553994
    Name: Full Text Finder (for New FTF UI) (s8985755)
    Category: fullText
    Text: Find It @ SCU Libraries
    MouseOverText: Find It @ SCU Libraries
  – Url: https://doaj.org/article/909a51ee968d491cb7336a83d534599b
    Name: EDS - DOAJ (s8985755)
    Category: fullText
    Text: View record from DOAJ
    MouseOverText: View record from DOAJ
Header DbId: edsdoj
DbLabel: Directory of Open Access Journals
An: edsdoj.909a51ee968d491cb7336a83d534599b
RelevancyScore: 919
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 918.959655761719
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells Through the Inhibition of Rac1
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Gerco+den+Hartog%22">Gerco den Hartog</searchLink><br /><searchLink fieldCode="AR" term="%22Lindsay+D%2E+Butcher%22">Lindsay D. Butcher</searchLink><br /><searchLink fieldCode="AR" term="%22Amber+L%2E+Ablack%22">Amber L. Ablack</searchLink><br /><searchLink fieldCode="AR" term="%22Laura+A%2E+Pace%22">Laura A. Pace</searchLink><br /><searchLink fieldCode="AR" term="%22Jailal+N%2E+G%2E+Ablack%22">Jailal N. G. Ablack</searchLink><br /><searchLink fieldCode="AR" term="%22Richard+Xiong%22">Richard Xiong</searchLink><br /><searchLink fieldCode="AR" term="%22Soumita+Das%22">Soumita Das</searchLink><br /><searchLink fieldCode="AR" term="%22Thaddeus+S%2E+Stappenbeck%22">Thaddeus S. Stappenbeck</searchLink><br /><searchLink fieldCode="AR" term="%22Lars+Eckmann%22">Lars Eckmann</searchLink><br /><searchLink fieldCode="AR" term="%22Peter+B%2E+Ernst%22">Peter B. Ernst</searchLink><br /><searchLink fieldCode="AR" term="%22Sheila+E%2E+Crowe%22">Sheila E. Crowe</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Frontiers in Immunology, Vol 11 (2021)
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: Frontiers Media S.A., 2021.
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2021
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: LCC:Immunologic diseases. Allergy
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22intestinal+epithelial+barrier%22">intestinal epithelial barrier</searchLink><br /><searchLink fieldCode="DE" term="%22invasion%22">invasion</searchLink><br /><searchLink fieldCode="DE" term="%22internalization%22">internalization</searchLink><br /><searchLink fieldCode="DE" term="%22Rac1%22">Rac1</searchLink><br /><searchLink fieldCode="DE" term="%22Salmonella+Typhimurium%22">Salmonella Typhimurium</searchLink><br /><searchLink fieldCode="DE" term="%22AIEC+LF82+strain%22">AIEC LF82 strain</searchLink><br /><searchLink fieldCode="DE" term="%22Immunologic+diseases%2E+Allergy%22">Immunologic diseases. Allergy</searchLink><br /><searchLink fieldCode="DE" term="%22RC581-607%22">RC581-607</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected with Salmonella enterica serovar Typhimurium or adherent-invasive Escherichia coli. The effects of APE1 inhibition on bacterial internalization, the regulation of Rho GTPase Rac1 as well as the epithelial cell barrier function were assessed. Increased numbers of bacteria were present in APE1-deficient colonic tumor cell lines and primary epithelial cells. Activation of Rac1 was augmented following infection but negatively regulated by APE1. Pharmacological inhibition of Rac1 reversed the increase in intracellular bacteria in APE1-deficient cells whereas overexpression of constitutively active Rac1 augmented the numbers in APE1-competent cells. Enhanced numbers of intracellular bacteria resulted in the loss of barrier function and a delay in its recovery. Our data demonstrate that APE1 inhibits the internalization of invasive bacteria into human intestinal epithelial cells through its ability to negatively regulate Rac1. This activity also protects epithelial cell barrier function.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article
– Name: Format
  Label: File Description
  Group: SrcInfo
  Data: electronic resource
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 1664-3224
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
  Data: https://www.frontiersin.org/articles/10.3389/fimmu.2020.553994/full; https://doaj.org/toc/1664-3224
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.3389/fimmu.2020.553994
– Name: URL
  Label: Access URL
  Group: URL
  Data: <link linkTarget="URL" linkTerm="https://doaj.org/article/909a51ee968d491cb7336a83d534599b" linkWindow="_blank">https://doaj.org/article/909a51ee968d491cb7336a83d534599b</link>
– Name: AN
  Label: Accession Number
  Group: ID
  Data: edsdoj.909a51ee968d491cb7336a83d534599b
PLink https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.909a51ee968d491cb7336a83d534599b
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.3389/fimmu.2020.553994
    Languages:
      – Text: English
    Subjects:
      – SubjectFull: intestinal epithelial barrier
        Type: general
      – SubjectFull: invasion
        Type: general
      – SubjectFull: internalization
        Type: general
      – SubjectFull: Rac1
        Type: general
      – SubjectFull: Salmonella Typhimurium
        Type: general
      – SubjectFull: AIEC LF82 strain
        Type: general
      – SubjectFull: Immunologic diseases. Allergy
        Type: general
      – SubjectFull: RC581-607
        Type: general
    Titles:
      – TitleFull: Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells Through the Inhibition of Rac1
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Gerco den Hartog
      – PersonEntity:
          Name:
            NameFull: Lindsay D. Butcher
      – PersonEntity:
          Name:
            NameFull: Amber L. Ablack
      – PersonEntity:
          Name:
            NameFull: Laura A. Pace
      – PersonEntity:
          Name:
            NameFull: Jailal N. G. Ablack
      – PersonEntity:
          Name:
            NameFull: Richard Xiong
      – PersonEntity:
          Name:
            NameFull: Soumita Das
      – PersonEntity:
          Name:
            NameFull: Thaddeus S. Stappenbeck
      – PersonEntity:
          Name:
            NameFull: Lars Eckmann
      – PersonEntity:
          Name:
            NameFull: Peter B. Ernst
      – PersonEntity:
          Name:
            NameFull: Sheila E. Crowe
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 02
              Type: published
              Y: 2021
          Identifiers:
            – Type: issn-print
              Value: 16643224
          Numbering:
            – Type: volume
              Value: 11
          Titles:
            – TitleFull: Frontiers in Immunology
              Type: main
ResultId 1