Interleukin-8 gene regulation in epithelial cells by Vibrio cholerae

Role of multiple promoter elements, adherence and motility of bacteria and host MAPKs

Madhubanti Sarkar, Swati Bhowmick, Antonella Casola, Keya Chaudhuri

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Interleukin (IL)-8 is an important mediator in neutrophil-mediated acute inflammation. We previously demonstrated that incubation of intestinal epithelial cells with Vibrio cholerae O395 resulted in increased IL-8 mRNA expression and IL-8 secretion, which was associated with the adherence and motility of bacteria. However, the mechanisms responsible for transcriptional regulation of the IL-8 gene in epithelial cells during V. cholerae infections were not explored. Transient transfection analysis of 5′ deletions and mutations of the IL-8 promoter driving expression of the luciferase reporter gene indicates that multiple binding sites contribute to IL-8 promoter induction in response to V. cholerae and that cooperation among these different sites is required for full activation of the promoter. Stimulation with V. cholerae O395 insertional mutants, defective in adherence and motility, significantly reduced IL-8 promoter activity compared with the wild-type strain. We further demonstrate maximal involvement of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase pathways to regulate IL-8 gene transcription. This study will help to design agents which could reduce the V. cholerae-induced inflammatory response and in the generation of safe vaccines.

Original languageEnglish (US)
Pages (from-to)1464-1473
Number of pages10
JournalFEBS Journal
Volume279
Issue number8
DOIs
StatePublished - Apr 2012

Fingerprint

Vibrio cholerae
Interleukin-8
Gene expression
Bacteria
Epithelial Cells
Genes
Vibrio Infections
Mitogen-Activated Protein Kinase 3
Sequence Deletion
Mitogen-Activated Protein Kinase 1
Transcription
Mitogen-Activated Protein Kinases
Luciferases
Reporter Genes
Transient analysis
Transfection
Neutrophils
Vaccines
Chemical activation
Binding Sites

Keywords

  • AP-1
  • IL-8
  • MAPK
  • NF-κB
  • Vibrio cholerae

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Interleukin-8 gene regulation in epithelial cells by Vibrio cholerae : Role of multiple promoter elements, adherence and motility of bacteria and host MAPKs. / Sarkar, Madhubanti; Bhowmick, Swati; Casola, Antonella; Chaudhuri, Keya.

In: FEBS Journal, Vol. 279, No. 8, 04.2012, p. 1464-1473.

Research output: Contribution to journalArticle

@article{ad0a22d247474fff8b4ddeae4b434317,
title = "Interleukin-8 gene regulation in epithelial cells by Vibrio cholerae: Role of multiple promoter elements, adherence and motility of bacteria and host MAPKs",
abstract = "Interleukin (IL)-8 is an important mediator in neutrophil-mediated acute inflammation. We previously demonstrated that incubation of intestinal epithelial cells with Vibrio cholerae O395 resulted in increased IL-8 mRNA expression and IL-8 secretion, which was associated with the adherence and motility of bacteria. However, the mechanisms responsible for transcriptional regulation of the IL-8 gene in epithelial cells during V. cholerae infections were not explored. Transient transfection analysis of 5′ deletions and mutations of the IL-8 promoter driving expression of the luciferase reporter gene indicates that multiple binding sites contribute to IL-8 promoter induction in response to V. cholerae and that cooperation among these different sites is required for full activation of the promoter. Stimulation with V. cholerae O395 insertional mutants, defective in adherence and motility, significantly reduced IL-8 promoter activity compared with the wild-type strain. We further demonstrate maximal involvement of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase pathways to regulate IL-8 gene transcription. This study will help to design agents which could reduce the V. cholerae-induced inflammatory response and in the generation of safe vaccines.",
keywords = "AP-1, IL-8, MAPK, NF-κB, Vibrio cholerae",
author = "Madhubanti Sarkar and Swati Bhowmick and Antonella Casola and Keya Chaudhuri",
year = "2012",
month = "4",
doi = "10.1111/j.1742-4658.2012.08539.x",
language = "English (US)",
volume = "279",
pages = "1464--1473",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Interleukin-8 gene regulation in epithelial cells by Vibrio cholerae

T2 - Role of multiple promoter elements, adherence and motility of bacteria and host MAPKs

AU - Sarkar, Madhubanti

AU - Bhowmick, Swati

AU - Casola, Antonella

AU - Chaudhuri, Keya

PY - 2012/4

Y1 - 2012/4

N2 - Interleukin (IL)-8 is an important mediator in neutrophil-mediated acute inflammation. We previously demonstrated that incubation of intestinal epithelial cells with Vibrio cholerae O395 resulted in increased IL-8 mRNA expression and IL-8 secretion, which was associated with the adherence and motility of bacteria. However, the mechanisms responsible for transcriptional regulation of the IL-8 gene in epithelial cells during V. cholerae infections were not explored. Transient transfection analysis of 5′ deletions and mutations of the IL-8 promoter driving expression of the luciferase reporter gene indicates that multiple binding sites contribute to IL-8 promoter induction in response to V. cholerae and that cooperation among these different sites is required for full activation of the promoter. Stimulation with V. cholerae O395 insertional mutants, defective in adherence and motility, significantly reduced IL-8 promoter activity compared with the wild-type strain. We further demonstrate maximal involvement of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase pathways to regulate IL-8 gene transcription. This study will help to design agents which could reduce the V. cholerae-induced inflammatory response and in the generation of safe vaccines.

AB - Interleukin (IL)-8 is an important mediator in neutrophil-mediated acute inflammation. We previously demonstrated that incubation of intestinal epithelial cells with Vibrio cholerae O395 resulted in increased IL-8 mRNA expression and IL-8 secretion, which was associated with the adherence and motility of bacteria. However, the mechanisms responsible for transcriptional regulation of the IL-8 gene in epithelial cells during V. cholerae infections were not explored. Transient transfection analysis of 5′ deletions and mutations of the IL-8 promoter driving expression of the luciferase reporter gene indicates that multiple binding sites contribute to IL-8 promoter induction in response to V. cholerae and that cooperation among these different sites is required for full activation of the promoter. Stimulation with V. cholerae O395 insertional mutants, defective in adherence and motility, significantly reduced IL-8 promoter activity compared with the wild-type strain. We further demonstrate maximal involvement of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase pathways to regulate IL-8 gene transcription. This study will help to design agents which could reduce the V. cholerae-induced inflammatory response and in the generation of safe vaccines.

KW - AP-1

KW - IL-8

KW - MAPK

KW - NF-κB

KW - Vibrio cholerae

UR - http://www.scopus.com/inward/record.url?scp=84859594456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859594456&partnerID=8YFLogxK

U2 - 10.1111/j.1742-4658.2012.08539.x

DO - 10.1111/j.1742-4658.2012.08539.x

M3 - Article

VL - 279

SP - 1464

EP - 1473

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 8

ER -