GRO-α regulation in airway smooth muscle by IL-1β and TNF-α: Role of NF-κB and MAP kinases

Razao Issa, Shaoping Xie, Kang Yun Lee, Rex D. Stanbridge, Pankaj Bhavsar, Maria B. Sukkar, Kian Fan Chung

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Airway smooth muscle cells (ASMC) are a source of inflammatory chemokines that may propagate airway inflammatory responses. We investigated the production of the CXC chemokine growth-related oncogene protein-α (GRO-α) from ASMC induced by cytokines and the role of MAPK and NF-κB pathways. ASMC were cultured from human airways, grown to confluence, and exposed to cytokines IL-1β and TNF-α after growth arrest. GRO-α release, measured by ELISA, was increased by >50-fold after IL-1β (0.1 ng/ml) or 5-fold after TNF-α (1 ng/ml) in a dose- and time-dependent manner. GRO-α release was not affected by the T helper type 2 cytokines IL-4, IL-10, and IL-13. IL-1β and TNF-α also induced GRO-α mRNA expression. Supernatants from IL-1β-stimulated ASMC were chemotactic for neutrophils; this effect was inhibited by anti-GRO-α blocking antibody. AS-602868, an inhibitor of IKK-2, and PD-98059, an inhibitor of ERK, inhibited GRO-α release and mRNA expression, whereas SP-600125, an inhibitor of JNK, reduced GRO-α release without effect on mRNA expression. SB-203580, an inhibitor of p38 MAPK, had no effect. AS-602868 but not PD-98059 or SP-600125 inhibited p65 DNA-binding induced by IL-1β and TNF-α. By chromatin immunoprecipitation assay, IL-1β and TNF-α enhanced p65 binding to the GRO-α promoter, which was inhibited by AS-602868. IL-1β- and TNF-α-stimulated expression of GRO-α from ASMC is regulated by independent pathways involving NF-κB activation and ERK and JNK pathways. GRO-α released from ASMC participates in neutrophil chemotaxis.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number1
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint

Oncogene Proteins
Interleukin-1
Smooth Muscle
Phosphotransferases
Growth
Smooth Muscle Myocytes
MAP Kinase Signaling System
Cytokines
Messenger RNA
Neutrophils
CXC Chemokines
Blocking Antibodies
Interleukin-13
Chromatin Immunoprecipitation
p38 Mitogen-Activated Protein Kinases
Chemotaxis
Chemokines
Interleukin-4
Interleukin-10
Enzyme-Linked Immunosorbent Assay

Keywords

  • c-Jun NH-terminal kinase
  • Extracellular signal-regulated kinase
  • Growth-related oncogene protein-α
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

GRO-α regulation in airway smooth muscle by IL-1β and TNF-α : Role of NF-κB and MAP kinases. / Issa, Razao; Xie, Shaoping; Lee, Kang Yun; Stanbridge, Rex D.; Bhavsar, Pankaj; Sukkar, Maria B.; Chung, Kian Fan.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 1, 2006.

Research output: Contribution to journalArticle

Issa, Razao ; Xie, Shaoping ; Lee, Kang Yun ; Stanbridge, Rex D. ; Bhavsar, Pankaj ; Sukkar, Maria B. ; Chung, Kian Fan. / GRO-α regulation in airway smooth muscle by IL-1β and TNF-α : Role of NF-κB and MAP kinases. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2006 ; Vol. 291, No. 1.
@article{2d640ca68d8d4408b27b8797c4f2201b,
title = "GRO-α regulation in airway smooth muscle by IL-1β and TNF-α: Role of NF-κB and MAP kinases",
abstract = "Airway smooth muscle cells (ASMC) are a source of inflammatory chemokines that may propagate airway inflammatory responses. We investigated the production of the CXC chemokine growth-related oncogene protein-α (GRO-α) from ASMC induced by cytokines and the role of MAPK and NF-κB pathways. ASMC were cultured from human airways, grown to confluence, and exposed to cytokines IL-1β and TNF-α after growth arrest. GRO-α release, measured by ELISA, was increased by >50-fold after IL-1β (0.1 ng/ml) or 5-fold after TNF-α (1 ng/ml) in a dose- and time-dependent manner. GRO-α release was not affected by the T helper type 2 cytokines IL-4, IL-10, and IL-13. IL-1β and TNF-α also induced GRO-α mRNA expression. Supernatants from IL-1β-stimulated ASMC were chemotactic for neutrophils; this effect was inhibited by anti-GRO-α blocking antibody. AS-602868, an inhibitor of IKK-2, and PD-98059, an inhibitor of ERK, inhibited GRO-α release and mRNA expression, whereas SP-600125, an inhibitor of JNK, reduced GRO-α release without effect on mRNA expression. SB-203580, an inhibitor of p38 MAPK, had no effect. AS-602868 but not PD-98059 or SP-600125 inhibited p65 DNA-binding induced by IL-1β and TNF-α. By chromatin immunoprecipitation assay, IL-1β and TNF-α enhanced p65 binding to the GRO-α promoter, which was inhibited by AS-602868. IL-1β- and TNF-α-stimulated expression of GRO-α from ASMC is regulated by independent pathways involving NF-κB activation and ERK and JNK pathways. GRO-α released from ASMC participates in neutrophil chemotaxis.",
keywords = "c-Jun NH-terminal kinase, Extracellular signal-regulated kinase, Growth-related oncogene protein-α, Nuclear factor-κB",
author = "Razao Issa and Shaoping Xie and Lee, {Kang Yun} and Stanbridge, {Rex D.} and Pankaj Bhavsar and Sukkar, {Maria B.} and Chung, {Kian Fan}",
year = "2006",
doi = "10.1152/ajplung.00384.2005",
language = "English",
volume = "291",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - GRO-α regulation in airway smooth muscle by IL-1β and TNF-α

T2 - Role of NF-κB and MAP kinases

AU - Issa, Razao

AU - Xie, Shaoping

AU - Lee, Kang Yun

AU - Stanbridge, Rex D.

AU - Bhavsar, Pankaj

AU - Sukkar, Maria B.

AU - Chung, Kian Fan

PY - 2006

Y1 - 2006

N2 - Airway smooth muscle cells (ASMC) are a source of inflammatory chemokines that may propagate airway inflammatory responses. We investigated the production of the CXC chemokine growth-related oncogene protein-α (GRO-α) from ASMC induced by cytokines and the role of MAPK and NF-κB pathways. ASMC were cultured from human airways, grown to confluence, and exposed to cytokines IL-1β and TNF-α after growth arrest. GRO-α release, measured by ELISA, was increased by >50-fold after IL-1β (0.1 ng/ml) or 5-fold after TNF-α (1 ng/ml) in a dose- and time-dependent manner. GRO-α release was not affected by the T helper type 2 cytokines IL-4, IL-10, and IL-13. IL-1β and TNF-α also induced GRO-α mRNA expression. Supernatants from IL-1β-stimulated ASMC were chemotactic for neutrophils; this effect was inhibited by anti-GRO-α blocking antibody. AS-602868, an inhibitor of IKK-2, and PD-98059, an inhibitor of ERK, inhibited GRO-α release and mRNA expression, whereas SP-600125, an inhibitor of JNK, reduced GRO-α release without effect on mRNA expression. SB-203580, an inhibitor of p38 MAPK, had no effect. AS-602868 but not PD-98059 or SP-600125 inhibited p65 DNA-binding induced by IL-1β and TNF-α. By chromatin immunoprecipitation assay, IL-1β and TNF-α enhanced p65 binding to the GRO-α promoter, which was inhibited by AS-602868. IL-1β- and TNF-α-stimulated expression of GRO-α from ASMC is regulated by independent pathways involving NF-κB activation and ERK and JNK pathways. GRO-α released from ASMC participates in neutrophil chemotaxis.

AB - Airway smooth muscle cells (ASMC) are a source of inflammatory chemokines that may propagate airway inflammatory responses. We investigated the production of the CXC chemokine growth-related oncogene protein-α (GRO-α) from ASMC induced by cytokines and the role of MAPK and NF-κB pathways. ASMC were cultured from human airways, grown to confluence, and exposed to cytokines IL-1β and TNF-α after growth arrest. GRO-α release, measured by ELISA, was increased by >50-fold after IL-1β (0.1 ng/ml) or 5-fold after TNF-α (1 ng/ml) in a dose- and time-dependent manner. GRO-α release was not affected by the T helper type 2 cytokines IL-4, IL-10, and IL-13. IL-1β and TNF-α also induced GRO-α mRNA expression. Supernatants from IL-1β-stimulated ASMC were chemotactic for neutrophils; this effect was inhibited by anti-GRO-α blocking antibody. AS-602868, an inhibitor of IKK-2, and PD-98059, an inhibitor of ERK, inhibited GRO-α release and mRNA expression, whereas SP-600125, an inhibitor of JNK, reduced GRO-α release without effect on mRNA expression. SB-203580, an inhibitor of p38 MAPK, had no effect. AS-602868 but not PD-98059 or SP-600125 inhibited p65 DNA-binding induced by IL-1β and TNF-α. By chromatin immunoprecipitation assay, IL-1β and TNF-α enhanced p65 binding to the GRO-α promoter, which was inhibited by AS-602868. IL-1β- and TNF-α-stimulated expression of GRO-α from ASMC is regulated by independent pathways involving NF-κB activation and ERK and JNK pathways. GRO-α released from ASMC participates in neutrophil chemotaxis.

KW - c-Jun NH-terminal kinase

KW - Extracellular signal-regulated kinase

KW - Growth-related oncogene protein-α

KW - Nuclear factor-κB

UR - http://www.scopus.com/inward/record.url?scp=33745686068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745686068&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00384.2005

DO - 10.1152/ajplung.00384.2005

M3 - Article

C2 - 16617094

AN - SCOPUS:33745686068

VL - 291

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 1

ER -