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Inhibition of p38 MAPK Reduces Expression of Vascular Endothelial Growth Factor in Allergic Airway Disease

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Abstract

Background

The p38 mitogen-activated protein kinase (MAPK) appears to play an important role in various pathophysiological responses and has been suggested to be involved in many processes considered critical to the inflammatory response and tissue remodeling. Bronchial asthma is a chronic inflammatory disorder of the airway accompanied by increased vascular permeability. Vascular endothelial growth factor (VEGF) is a potent stimulator of bronchial inflammation, airway remodeling, and physiologic dysregulation that augments antigen sensitization and T-helper type 2 cell (Th2)-mediated inflammation in allergic airway diseases. However, there are little data on the relationship between p38 MAPK signaling and VEGF expression in allergic airway disease.

Objective

This study aimed to investigate the role of p38 MAPK on the pathogenesis of allergic airway disease, more specifically in VEGF expression.

Methods

Using ovalbumin (OVA)-inhaled mice and a selective p38 MAPK inhibitor, SB 239063, the involvement of p38 MAPK in allergen-induced VEGF expression in the airway was evaluated.

Results

The increases of phosphorylation of p38 MAPK, VEGF protein expression, and vascular permeability in the lung after OVA inhalation were decreased substantially by the administration of SB 239063. In addition, SB 239063 significantly reduced the increase of Th2 cytokines and OVA-specific IgE. The inhibition of p38 MAPK or VEGF signaling prevented and also decreased the increases in the number of inflammatory cells and airway hyperresponsiveness in OVA-induced allergic airway disease.

Conclusions

These results indicate that inhibition of p38 MAPK may attenuate allergen-induced airway inflammation and vascular leakage through modulation of VEGF expression in mice.

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Acknowledgments

We thank Professor Mie-Jae Im (Chonbuk National University Medical School, Jeonju, South Korea) for critical readings of the manuscript. This work was supported by the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea; Grant A084144 (to Yong Chul Lee) and Grant A111992 (to So Ri Kim).

Conflict of interest

The authors declare that they have no conflict of financial interests.

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Authors and Affiliations

  1. Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, South Korea

    So Ri Kim, Kyung Sun Lee, Seoung Ju Park, Myung Shin Jeon & Yong Chul Lee

  2. Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, 561-180, South Korea

    Yong Chul Lee

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  1. So Ri Kim
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Correspondence to Yong Chul Lee.

Additional information

So Ri Kim and Kyung Sun Lee contributed equally to this work.

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Kim, S.R., Lee, K.S., Park, S.J. et al. Inhibition of p38 MAPK Reduces Expression of Vascular Endothelial Growth Factor in Allergic Airway Disease. J Clin Immunol 32, 574–586 (2012). https://doi.org/10.1007/s10875-012-9672-5

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  • DOI: https://doi.org/10.1007/s10875-012-9672-5

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