A small-molecule compound targeting CCR5 and CXCR3 prevents the development of asthma

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

^* To whom correspondence should be addressed. E-mail: khamada{at}naramed-u.ac.jp.

	Abstract

Asthma is associated with increased number of T cells in the lung. CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 3 (CXCR3) have been reported to play important roles in lung T cell homing pathway, and may be potential targets for asthma therapy.

The aim of this study was to investigate a 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.

We sensitized mice with ovalbumin (OVA). We measured mRNA expression of chemokine receptors in the lung after the challenge with either aerosolized PBS or OVA. We also treated OVA-sensitized mice with TAK-779. We measured respiratory function, performed bronchoalveolar lavage, and obtained blood and lung.

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 CCR5 and CXCR3 using TAK-779, a synthetic non-peptide compound, can prevent the development of asthma features in a mouse model. Thus, CCR5 and CXCR3 may be potential targets for asthma therapy.

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