- Paper Report
- Open Access
TARC attenuates the development of asthma in mice
- Yassine Amrani1
© Biomed Central Ltd 2001
- Received: 7 March 2001
- Accepted: 18 September 2001
- Published: 18 September 2001
- Airway inflammation, allergen, CD4+ lymphocytes, chemokines, eosinophils, eotaxin, TARC
Evidence now suggests that chemokines such as RANTES (regulated on activation normal T cell expressed and secreted) and eotaxin may play an important role in mediating lung inflammation in asthma. However, the precise nature of the different chemokines involved is not fully defined. Thymus- and activation-regulated chemokine (TARC), which specifically binds to the CC chemokine receptor 4 (CCR4), is an interesting candidate as it regulates the chemotaxis of CD4+ T lymphocytes that are active cells in the pathogenesis of asthma. In this study, the authors investigated whether TARC is involved in the development of airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma.
TARC mRNA levels in the lungs increased significantly at 3, 6, 24 and 48 h after allergen challenge. Immunohistochemical staining also showed an increased expression of TARC protein in lung sections of allergen-challenged mice, with staining mainly located in the bronchial epithelium and endothelium. When compared to control antibody anti-TARC antibody blocked the OVA-induced increase in eosinophils and CD4+ T lymphocytes in both bronchoalveolar lavage (BAL) and lung tissue. Anti-TARC antibody also abrogated the elevated production of interleukin (IL)-4, IL-13 and interferon-g found in BAL and the increase in eotaxin gene expression found in the lung of OVA-challenged mice. Finally, the anti-TARC antibody resulted in a 64% inhibition of allergen-induced increases in AHR to methacholine. Collectively, these data showed the involvement of TARC in regulating eosinophilia and AHR in an animal model of asthma.
Animal sensitization, RT-PCR, immunostaining, ELISA, airway responsiveness
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