Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells

Adam J. Ratner, Ruth Bryan, Adam Weber, Stephen Nguyen, Derrick Barnes, Allyson Pitt, Shari Gelber, Ambrose Cheung, Alice Prince

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa and Staphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants and S. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca 2+]i in 1HAEo- airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-κB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca2+ release activated this pathway, whereas P. aeruginosa lipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.

Original languageEnglish (US)
Pages (from-to)19267-19275
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number22
DOIs
StatePublished - Jun 1 2001
Externally publishedYes

Fingerprint

Pathogens
Mitogen-Activated Protein Kinases
Interleukin-8
Cystic Fibrosis
Pseudomonas aeruginosa
Epithelial Cells
Ligation
Staphylococcus aureus
Chemical activation
Cystic Fibrosis Transmembrane Conductance Regulator
Pulmonary diseases
Thapsigargin
Mitogen-Activated Protein Kinase 1
Chemokines
Bacterial Infections
Lung Diseases
Lipopolysaccharides
Bacteria
Neutrophils
Epithelium

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells. / Ratner, Adam J.; Bryan, Ruth; Weber, Adam; Nguyen, Stephen; Barnes, Derrick; Pitt, Allyson; Gelber, Shari; Cheung, Ambrose; Prince, Alice.

In: Journal of Biological Chemistry, Vol. 276, No. 22, 01.06.2001, p. 19267-19275.

Research output: Contribution to journalArticle

Ratner, AJ, Bryan, R, Weber, A, Nguyen, S, Barnes, D, Pitt, A, Gelber, S, Cheung, A & Prince, A 2001, 'Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells', Journal of Biological Chemistry, vol. 276, no. 22, pp. 19267-19275. https://doi.org/10.1074/jbc.M007703200
Ratner, Adam J. ; Bryan, Ruth ; Weber, Adam ; Nguyen, Stephen ; Barnes, Derrick ; Pitt, Allyson ; Gelber, Shari ; Cheung, Ambrose ; Prince, Alice. / Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 22. pp. 19267-19275.
@article{58d631cdf2a44de4aa279ea7ff05892f,
title = "Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells",
abstract = "Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa and Staphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants and S. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca 2+]i in 1HAEo- airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-κB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca2+ release activated this pathway, whereas P. aeruginosa lipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.",
author = "Ratner, {Adam J.} and Ruth Bryan and Adam Weber and Stephen Nguyen and Derrick Barnes and Allyson Pitt and Shari Gelber and Ambrose Cheung and Alice Prince",
year = "2001",
month = "6",
day = "1",
doi = "10.1074/jbc.M007703200",
language = "English (US)",
volume = "276",
pages = "19267--19275",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "22",

}

TY - JOUR

T1 - Cystic Fibrosis Pathogens Activate Ca2+-dependent Mitogen-activated Protein Kinase Signaling Pathways in Airway Epithelial Cells

AU - Ratner, Adam J.

AU - Bryan, Ruth

AU - Weber, Adam

AU - Nguyen, Stephen

AU - Barnes, Derrick

AU - Pitt, Allyson

AU - Gelber, Shari

AU - Cheung, Ambrose

AU - Prince, Alice

PY - 2001/6/1

Y1 - 2001/6/1

N2 - Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa and Staphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants and S. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca 2+]i in 1HAEo- airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-κB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca2+ release activated this pathway, whereas P. aeruginosa lipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.

AB - Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa and Staphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants and S. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca 2+]i in 1HAEo- airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-κB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca2+ release activated this pathway, whereas P. aeruginosa lipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.

UR - http://www.scopus.com/inward/record.url?scp=0035374513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035374513&partnerID=8YFLogxK

U2 - 10.1074/jbc.M007703200

DO - 10.1074/jbc.M007703200

M3 - Article

VL - 276

SP - 19267

EP - 19275

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 22

ER -