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Chemokine receptor 3 (Ccr3) plays an important role in allergic rhinitis induced by toluene diisocyanate.
Johnson-VJ; Kashon-ML; Yucesoy-B; Reynolds-JS; Luster-MI
Am J Respir Crit Care Med 2008 Apr; 177(Meeting Abstracts):A297
Rhinitis often precedes and is a co-existing disease in workers with occupational asthma. Therefore, understanding occupational rhinitis may result in new diagnostic and therapeutic strategies that may help prevent the development of asthma. We previously developed a murine model of toluene diisocyanate (TDI) rhinitis displaying increased expression of IL-4, IL-5, IL-13, IFNGamma, TNFalpha and IL-1Beta as well as extensive eosinophil infiltration into the nasal mucosa. Whole-genome expression analysis demonstrated that genes involved in inflammatory cell recruitment/movement and, specifically, chemotaxis, chemokine activation and chemokine receptor binding were differentially expressed in the nasal mucosa of mice with TDI rhinitis. The chemokine receptor 3 (Ccr3) pathway is important for the recruitment of eosinophils and Th2 lymphocytes to sites of allergic inflammation. We hypothesized that the Ccr3:ligand axis is activated in TDI rhinitis leading to the recruitment of Th2 lymphocytes and eosinophils. Mice were exposed to 50 ppb TDI vapor via inhalation for 12 consecutive weekdays and real-time PCR was used to analyze the expression of chemokine, chemokine receptor and immune genes in the nasal mucosa 24 hours following the final exposure. Expression of Ccr3 and its ligands, Ccl11 (eotaxin I) and Ccl24 (eotaxin II) were upregulated in the nasal mucosa following TDI inhalation. Administration of neutralizing anti-Ccr3 antibodies prior to TDI exposure prevented the upregulation of Ccl11 and Ccl24. In addition, neutralization of Ccr3 markedly reduced TDI-induced changes in IL-4, IL-5, IL-13, TNFAlpha and IL-1Beta expression. These results support the hypothesis that Ccr3 is an important mediator of inflammation in TDI rhinitis.
Respiratory-system-disorders; Pulmonary-system-disorders; Bronchial-asthma; Laboratory-animals; Animal-studies; Animals
American Journal of Respiratory and Critical Care Medicine
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