HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Suzaki, Y. Articles by Kimura, H. PubMed PubMed Citation Articles by Suzaki, Y. Articles by Kimura, H.

A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation

¹ Second Dept of Internal Medicine, and ² Dept of Surgery, Nara Medical University, Nara, Japan.

CORRESPONDENCE: K. Hamada, Second Dept of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara Nara 634-8522, Japan. Fax: 81 744290907. E-mail: khamada{at}naramed-u.ac.jp

Keywords: Asthma, CC chemokine receptor 5, chemokine, CXC chemokine receptor 3, cytokine

Received: August 25, 2007
Accepted November 29, 2007

Asthma is associated with increased numbers of T-cells in the lung. CC chemokine receptor (CCR)5 and CXC chemokine receptor (CXCR)3 have been reported to play important roles in the lung T-cell homing pathway, and may be potential targets for asthma therapy. The aim of the present study was to investigate the role of CCR5 and CXCR3 in allergen-induced acute asthma and to determine whether a novel small-molecule compound, TAK-779, targeting CCR5 and CXCR3 can attenuate allergic airway responses.

Mice were sensitised with ovalbumin (OVA). mRNA expression of chemokine receptors in the lung were measured after the challenge with either aerosolised phosphate-buffered saline or OVA. OVA-sensitised mice were also treated with TAK-779. Respiratory function was measured, bronchoalveolar lavage was performed, and blood and lung samples were obtained.

OVA challenge increased CCR3, CCR5 and CXCR3 expression in the lung. Treatment with TAK-779 significantly attenuated altered respiratory function and pulmonary allergic inflammation. The beneficial effect was associated with reduced expression of CCR5 and CXCR3 in the lung.

These data demonstrate that blockade of CC chemokine receptor 5 and CXC chemokine receptor 3 using TAK-779, a synthetic nonpeptide compound, can prevent the development of asthma features in a mouse model. Thus, CC chemokine receptor 5 and CXC chemokine receptor 3 may be potential targets for asthma therapy.