Induction of interleukin 8 by American cockroach allergens from human airway epithelial cells via extracellular signal regulatory kinase and jun N-terminal kinase but not p38 mitogen-activated protein kinase

Mey Fann Lee, Nancy M. Wang, Szu Wei Liu, Shyh Jye Lin, Yi Hsing Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G proteinlinked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. Objective To investigate the mechanisms of American cockroach allergens (CraA) on interleukin 8 (IL-8) in human pulmonary epithelial cells. Methods Protease activities of CraA were quantified by the Azocoll method. The gene and protein expressions of IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) was assessed by Western blot. Results CraA-induced A549 cell IL-8 secretion in a dose-dependent manner at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and aprotinin but not by other protease inhibitors. Blocking antibodies against the cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8 production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK) phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125) inhibitors inhibited CraA-induced IL-8 secretion by 100% and 45%, respectively. Conclusions Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8 secretion from human airway epithelial cells. It signals mainly through the ERK1/2 and partly from the JNK pathways. The key receptors and signaling molecules mediate cytokine release from the respiratory epithelium and can be potential therapeutic targets in treating cockroach allergy.

Original languageEnglish
Pages (from-to)234-240
Number of pages7
JournalAnnals of Allergy, Asthma and Immunology
Volume105
Issue number3
DOIs
Publication statusPublished - 2010 Sep 1

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Periplaneta
Cockroaches
p38 Mitogen-Activated Protein Kinases
Interleukin-8
Allergens
Phosphotransferases
Epithelial Cells
PAR-2 Receptor
Proteinase-Activated Receptors
PAR-1 Receptor
Respiratory Mucosa
Messenger RNA
Serine Proteinase Inhibitors
Aprotinin
Blocking Antibodies
Mitogen-Activated Protein Kinases
Protease Inhibitors
Real-Time Polymerase Chain Reaction
Hypersensitivity
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

@article{daf21a95f7a04f28935447e140a6da06,
title = "Induction of interleukin 8 by American cockroach allergens from human airway epithelial cells via extracellular signal regulatory kinase and jun N-terminal kinase but not p38 mitogen-activated protein kinase",
abstract = "Background Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G proteinlinked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. Objective To investigate the mechanisms of American cockroach allergens (CraA) on interleukin 8 (IL-8) in human pulmonary epithelial cells. Methods Protease activities of CraA were quantified by the Azocoll method. The gene and protein expressions of IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) was assessed by Western blot. Results CraA-induced A549 cell IL-8 secretion in a dose-dependent manner at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and aprotinin but not by other protease inhibitors. Blocking antibodies against the cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8 production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK) phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125) inhibitors inhibited CraA-induced IL-8 secretion by 100{\%} and 45{\%}, respectively. Conclusions Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8 secretion from human airway epithelial cells. It signals mainly through the ERK1/2 and partly from the JNK pathways. The key receptors and signaling molecules mediate cytokine release from the respiratory epithelium and can be potential therapeutic targets in treating cockroach allergy.",
author = "Lee, {Mey Fann} and Wang, {Nancy M.} and Liu, {Szu Wei} and Lin, {Shyh Jye} and Chen, {Yi Hsing}",
year = "2010",
month = "9",
day = "1",
doi = "10.1016/j.anai.2010.07.008",
language = "English",
volume = "105",
pages = "234--240",
journal = "Annals of Allergy, Asthma and Immunology",
issn = "1081-1206",
publisher = "American College of Allergy, Asthma and Immunology",
number = "3",

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TY - JOUR

T1 - Induction of interleukin 8 by American cockroach allergens from human airway epithelial cells via extracellular signal regulatory kinase and jun N-terminal kinase but not p38 mitogen-activated protein kinase

AU - Lee, Mey Fann

AU - Wang, Nancy M.

AU - Liu, Szu Wei

AU - Lin, Shyh Jye

AU - Chen, Yi Hsing

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Background Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G proteinlinked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. Objective To investigate the mechanisms of American cockroach allergens (CraA) on interleukin 8 (IL-8) in human pulmonary epithelial cells. Methods Protease activities of CraA were quantified by the Azocoll method. The gene and protein expressions of IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) was assessed by Western blot. Results CraA-induced A549 cell IL-8 secretion in a dose-dependent manner at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and aprotinin but not by other protease inhibitors. Blocking antibodies against the cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8 production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK) phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125) inhibitors inhibited CraA-induced IL-8 secretion by 100% and 45%, respectively. Conclusions Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8 secretion from human airway epithelial cells. It signals mainly through the ERK1/2 and partly from the JNK pathways. The key receptors and signaling molecules mediate cytokine release from the respiratory epithelium and can be potential therapeutic targets in treating cockroach allergy.

AB - Background Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G proteinlinked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. Objective To investigate the mechanisms of American cockroach allergens (CraA) on interleukin 8 (IL-8) in human pulmonary epithelial cells. Methods Protease activities of CraA were quantified by the Azocoll method. The gene and protein expressions of IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) was assessed by Western blot. Results CraA-induced A549 cell IL-8 secretion in a dose-dependent manner at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and aprotinin but not by other protease inhibitors. Blocking antibodies against the cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8 production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK) phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125) inhibitors inhibited CraA-induced IL-8 secretion by 100% and 45%, respectively. Conclusions Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8 secretion from human airway epithelial cells. It signals mainly through the ERK1/2 and partly from the JNK pathways. The key receptors and signaling molecules mediate cytokine release from the respiratory epithelium and can be potential therapeutic targets in treating cockroach allergy.

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U2 - 10.1016/j.anai.2010.07.008

DO - 10.1016/j.anai.2010.07.008

M3 - Article

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AN - SCOPUS:77956144506

VL - 105

SP - 234

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JO - Annals of Allergy, Asthma and Immunology

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SN - 1081-1206

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