Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma

Mark F. Sands, Patricia J. Ohtake, Supriya D. Mahajan, Shervin S. Takyar, Ravikumar Aalinkeel, Yisheng V. Fang, Jessica W. Blume, Barbara A. Mullan, Don E. Sykes, Sandra Lachina, Paul R. Knight, Stanley A. Schwartz

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.

Original languageEnglish (US)
Pages (from-to)186-198
Number of pages13
JournalClinical Immunology
Volume130
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Pneumonia
Asthma
Lung
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Cytokines
Inflammation
Lung Compliance
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 2
Ovalbumin
Collagen
Animal Models
Phenotype
Messenger RNA
Wounds and Injuries
Proteins

Keywords

  • Airway remodeling
  • Asthma
  • Bronchial hyperreactivity
  • Intercellular matrix
  • MMPs
  • TIMP-1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Sands, M. F., Ohtake, P. J., Mahajan, S. D., Takyar, S. S., Aalinkeel, R., Fang, Y. V., ... Schwartz, S. A. (2009). Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma. Clinical Immunology, 130(2), 186-198. https://doi.org/10.1016/j.clim.2008.08.029

Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma. / Sands, Mark F.; Ohtake, Patricia J.; Mahajan, Supriya D.; Takyar, Shervin S.; Aalinkeel, Ravikumar; Fang, Yisheng V.; Blume, Jessica W.; Mullan, Barbara A.; Sykes, Don E.; Lachina, Sandra; Knight, Paul R.; Schwartz, Stanley A.

In: Clinical Immunology, Vol. 130, No. 2, 02.2009, p. 186-198.

Research output: Contribution to journalArticle

Sands, MF, Ohtake, PJ, Mahajan, SD, Takyar, SS, Aalinkeel, R, Fang, YV, Blume, JW, Mullan, BA, Sykes, DE, Lachina, S, Knight, PR & Schwartz, SA 2009, 'Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma', Clinical Immunology, vol. 130, no. 2, pp. 186-198. https://doi.org/10.1016/j.clim.2008.08.029
Sands, Mark F. ; Ohtake, Patricia J. ; Mahajan, Supriya D. ; Takyar, Shervin S. ; Aalinkeel, Ravikumar ; Fang, Yisheng V. ; Blume, Jessica W. ; Mullan, Barbara A. ; Sykes, Don E. ; Lachina, Sandra ; Knight, Paul R. ; Schwartz, Stanley A. / Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma. In: Clinical Immunology. 2009 ; Vol. 130, No. 2. pp. 186-198.
@article{3b6118a6f59f40599f424808ed399b98,
title = "Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma",
abstract = "Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.",
keywords = "Airway remodeling, Asthma, Bronchial hyperreactivity, Intercellular matrix, MMPs, TIMP-1",
author = "Sands, {Mark F.} and Ohtake, {Patricia J.} and Mahajan, {Supriya D.} and Takyar, {Shervin S.} and Ravikumar Aalinkeel and Fang, {Yisheng V.} and Blume, {Jessica W.} and Mullan, {Barbara A.} and Sykes, {Don E.} and Sandra Lachina and Knight, {Paul R.} and Schwartz, {Stanley A.}",
year = "2009",
month = "2",
doi = "10.1016/j.clim.2008.08.029",
language = "English (US)",
volume = "130",
pages = "186--198",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma

AU - Sands, Mark F.

AU - Ohtake, Patricia J.

AU - Mahajan, Supriya D.

AU - Takyar, Shervin S.

AU - Aalinkeel, Ravikumar

AU - Fang, Yisheng V.

AU - Blume, Jessica W.

AU - Mullan, Barbara A.

AU - Sykes, Don E.

AU - Lachina, Sandra

AU - Knight, Paul R.

AU - Schwartz, Stanley A.

PY - 2009/2

Y1 - 2009/2

N2 - Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.

AB - Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.

KW - Airway remodeling

KW - Asthma

KW - Bronchial hyperreactivity

KW - Intercellular matrix

KW - MMPs

KW - TIMP-1

UR - http://www.scopus.com/inward/record.url?scp=58049112621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58049112621&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2008.08.029

DO - 10.1016/j.clim.2008.08.029

M3 - Article

C2 - 18955015

AN - SCOPUS:58049112621

VL - 130

SP - 186

EP - 198

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 2

ER -