Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model

Dae Yong Kim, Jung Won Park, Dooil Jeoung, Jai Youl Ro

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Celastrol has anti-inflammatory and immunomodulatory activities, but its anti-allergic effects remain poorly understood. Therefore, we aimed to investigate the ability of celastrol to inhibit asthmatic reactions in a mouse allergic asthma model. BALB/c mice were sensitized and challenged with ovalbumin to induce asthma. We measured the recruitment of inflammatory cells into the bronchoalveolar lavage fluid or lung tissues by Diff-Quik and hematoxylin and eosin staining, respectively, goblet cell hyperplasia by periodic acid-Schiff (PAS) staining, airway hyperresponsiveness by Flexvent system, mRNA and protein expression of cytokines, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) by reverse transcriptase polymerase chain reaction and ELISA, respectively, and the activities of mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-κB) in the bronchoalveolar lavage cells and lung tissues by Western blot and electrophoretic mobility shift assay (EMSA), respectively. Celastrol reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid and in peribronchial areas, and decreased the airway hyperresponsiveness, mRNA and protein expression levels for inflammatory cytokines such as interleukin (IL)-4, IL-13, TNF-α and IFN-γ, and for MMPs and TIMPs, MAP kinases and NF-κB activities in the bronchoalveolar lavage cells and in the lung tissues increased in ovalbumin-induced allergic asthma in mice. Our data suggest that oral administration of celastrol suppresses ovalbumin-induced airway inflammation, hyperresponsiveness, and tissue remodeling by regulating the imbalance of MMP-2/-9 and TIMP-1/-2 by inflammatory cytokines via MAP kinases/NF-κB in inflammatory cells. Based on our findings, we suggest that celastrol may be used as a therapeutic agent for allergy-induced asthma.

Original languageEnglish
Pages (from-to)98-105
Number of pages8
JournalEuropean Journal of Pharmacology
Volume612
Issue number1-3
DOIs
Publication statusPublished - 2009 Jun 10

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Allergens
Asthma
NF-kappa B
Inflammation
Ovalbumin
Mitogen-Activated Protein Kinases
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase Inhibitors
Bronchoalveolar Lavage Fluid
Bronchoalveolar Lavage
Cytokines
Lung
Staining and Labeling
Tissue Inhibitor of Metalloproteinase-2
Anti-Allergic Agents
Messenger RNA
Periodic Acid
Tissue Inhibitor of Metalloproteinase-1
Goblet Cells
Interleukin-13

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kim, Dae Yong ; Park, Jung Won ; Jeoung, Dooil ; Ro, Jai Youl. / Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model. In: European Journal of Pharmacology. 2009 ; Vol. 612, No. 1-3. pp. 98-105.
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abstract = "Celastrol has anti-inflammatory and immunomodulatory activities, but its anti-allergic effects remain poorly understood. Therefore, we aimed to investigate the ability of celastrol to inhibit asthmatic reactions in a mouse allergic asthma model. BALB/c mice were sensitized and challenged with ovalbumin to induce asthma. We measured the recruitment of inflammatory cells into the bronchoalveolar lavage fluid or lung tissues by Diff-Quik and hematoxylin and eosin staining, respectively, goblet cell hyperplasia by periodic acid-Schiff (PAS) staining, airway hyperresponsiveness by Flexvent system, mRNA and protein expression of cytokines, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) by reverse transcriptase polymerase chain reaction and ELISA, respectively, and the activities of mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-κB) in the bronchoalveolar lavage cells and lung tissues by Western blot and electrophoretic mobility shift assay (EMSA), respectively. Celastrol reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid and in peribronchial areas, and decreased the airway hyperresponsiveness, mRNA and protein expression levels for inflammatory cytokines such as interleukin (IL)-4, IL-13, TNF-α and IFN-γ, and for MMPs and TIMPs, MAP kinases and NF-κB activities in the bronchoalveolar lavage cells and in the lung tissues increased in ovalbumin-induced allergic asthma in mice. Our data suggest that oral administration of celastrol suppresses ovalbumin-induced airway inflammation, hyperresponsiveness, and tissue remodeling by regulating the imbalance of MMP-2/-9 and TIMP-1/-2 by inflammatory cytokines via MAP kinases/NF-κB in inflammatory cells. Based on our findings, we suggest that celastrol may be used as a therapeutic agent for allergy-induced asthma.",
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Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model. / Kim, Dae Yong; Park, Jung Won; Jeoung, Dooil; Ro, Jai Youl.

In: European Journal of Pharmacology, Vol. 612, No. 1-3, 10.06.2009, p. 98-105.

Research output: Contribution to journalArticle

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