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
KeywordsAirway 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.
The proteins RANTES and eotaxin may be involved in the pathogenesis of asthma by recruiting inflammatory cells within the airways. Here, the authors found no significant increase in RANTES expression in the lung of OVA-challenged animals contrasting with a previous report showing a potential role of RANTES in allergen-induced leukocyte infiltration in the airways of a murine model of asthma (see Additional information). In this study, however, TARC was found to play a major role in the accumulation of eosinophils and CD4+ T lymphocytes in the lungs of allergen-challenged mice, possibly through effects on the expression of Th2-type cytokines and eotaxin. The precise mechanism by which TARC is upregulated after allergen challenge has not been addressed here but the study demonstrates that the airway epithelium and endothelium are the most important cellular sources of TARC in the airways. As TARC modulates both airway inflammation and BHR, targeting TARC synthesis or activity in these cell types may offer new insights in the design of new treatments for asthma.
Animal sensitization, RT-PCR, immunostaining, ELISA, airway responsiveness
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