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Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma.
J Allergy Clin Immunol. 2004 May; 113(5):902-9.JA

Abstract

BACKGROUND

Toluene diisocyanate (TDI) is a leading cause of occupational asthma. Although considerable controversy remains regarding its pathogenesis, TDI-induced asthma is an inflammatory disease of the airways characterized by airway remodeling caused, at least in part, by an excess of extracellular matrix deposition in the airway wall. Matrix metalloproteinases (MMPs) are major proteolytic enzymes that are involved in extracellular matrix turnover because of their ability to cleave all proteins constituting extracellular matrix. Previous studies have reported that MMP-9 might play a role in chronic airway inflammation and remodeling in asthma.

OBJECTIVE

An aim of the current study was to evaluate the effects of MMP-inhibiting antibiotic, doxycycline, and MMP inhibitors on hyperresponsiveness and inflammation of the airways in TDI-induced asthma.

METHODS

We used a murine model for TDI-induced asthma to examine the effect of doxycycline or MMP inhibitors on bronchial inflammation and airway hyperresponsiveness.

RESULTS

The following typical pathophysiologic features are observed in the lungs of the mice: airway inflammation, airway hyperresponsiveness, and increased expression of MMP-9 mRNA and protein. Administration of doxycycline and MMP inhibitors reduced all of these pathophysiologic findings. In addition, the increased phosphorylated Akt but not Akt protein levels in lung tissues after TDI inhalation were significantly reduced by the administration of doxycycline and MMP inhibitors.

CONCLUSION

These findings suggest that doxycycline may reduce airway inflammation and hyperresponsiveness through phosphatidylinositol 3-kinase pathway in a murine model of TDI-induced asthma.

Authors+Show Affiliations

Lee KS
Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, 634-18 Keumamdong, Jeonju 561-712, South Korea.
Jin SM
No affiliation info available
Kim SS
No affiliation info available
Lee YC
No affiliation info available

MeSH

AnimalsAnti-Bacterial AgentsAsthmaBronchial HyperreactivityBronchoalveolar Lavage FluidDisease Models, AnimalDoxycyclineFemaleInflammationLungMatrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMiceMice, Inbred BALB COvalbuminProtease InhibitorsRNA, MessengerToluene 2,4-Diisocyanate

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15131573

Citation

Lee, Kyung S., et al. "Doxycycline Reduces Airway Inflammation and Hyperresponsiveness in a Murine Model of Toluene Diisocyanate-induced Asthma." The Journal of Allergy and Clinical Immunology, vol. 113, no. 5, 2004, pp. 902-9.
Lee KS, Jin SM, Kim SS, et al. Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma. J Allergy Clin Immunol. 2004;113(5):902-9.
Lee, K. S., Jin, S. M., Kim, S. S., & Lee, Y. C. (2004). Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma. The Journal of Allergy and Clinical Immunology, 113(5), 902-9.
Lee KS, et al. Doxycycline Reduces Airway Inflammation and Hyperresponsiveness in a Murine Model of Toluene Diisocyanate-induced Asthma. J Allergy Clin Immunol. 2004;113(5):902-9. PubMed PMID: 15131573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma. AU - Lee,Kyung S, AU - Jin,Sun M, AU - Kim,Seung S, AU - Lee,Yong C, PY - 2004/5/8/pubmed PY - 2004/6/18/medline PY - 2004/5/8/entrez SP - 902 EP - 9 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 113 IS - 5 N2 - BACKGROUND: Toluene diisocyanate (TDI) is a leading cause of occupational asthma. Although considerable controversy remains regarding its pathogenesis, TDI-induced asthma is an inflammatory disease of the airways characterized by airway remodeling caused, at least in part, by an excess of extracellular matrix deposition in the airway wall. Matrix metalloproteinases (MMPs) are major proteolytic enzymes that are involved in extracellular matrix turnover because of their ability to cleave all proteins constituting extracellular matrix. Previous studies have reported that MMP-9 might play a role in chronic airway inflammation and remodeling in asthma. OBJECTIVE: An aim of the current study was to evaluate the effects of MMP-inhibiting antibiotic, doxycycline, and MMP inhibitors on hyperresponsiveness and inflammation of the airways in TDI-induced asthma. METHODS: We used a murine model for TDI-induced asthma to examine the effect of doxycycline or MMP inhibitors on bronchial inflammation and airway hyperresponsiveness. RESULTS: The following typical pathophysiologic features are observed in the lungs of the mice: airway inflammation, airway hyperresponsiveness, and increased expression of MMP-9 mRNA and protein. Administration of doxycycline and MMP inhibitors reduced all of these pathophysiologic findings. In addition, the increased phosphorylated Akt but not Akt protein levels in lung tissues after TDI inhalation were significantly reduced by the administration of doxycycline and MMP inhibitors. CONCLUSION: These findings suggest that doxycycline may reduce airway inflammation and hyperresponsiveness through phosphatidylinositol 3-kinase pathway in a murine model of TDI-induced asthma. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/15131573/Doxycycline_reduces_airway_inflammation_and_hyperresponsiveness_in_a_murine_model_of_toluene_diisocyanate_induced_asthma_ DB - PRIME DP - Unbound Medicine ER -