Mechanisms of CpG-ODNs inhibiting the airway remodeling of chronic asthma in mice

Objective: To investigate the effect of CpG-oligodeoxynucleotides (CpG-ODNs) on airway remodeling in ovalbumin (OVA)-sensitized chronic asthmatic model in mice and the action mechanisms. Methods: Forty female Balb/c mice were randomly divided into saline group, OVA group, OVA+CpG-ODNs group, and OVA+GpC-ODNs group, with 10 in each. At the end of OVA exposure, mice were evaluated for the development of airway remodeling. Blood and bronchoalveolar lavage fluid (BAL) were collected for the measurement of OVA specific IgE, interleukin-4 (IL-4), interferon-γ (IFN-γ) , interleukin-10 (IL-10) and leukocytes count. Results: Mice exposed to recurrent airway OVA challenge had chronic inflammation and airway remodeling, including inflammatory cell infiltration, subepithelial collagen deposition, goblet cell hyperplasia-metaplasia and proliferation of airway smooth muscle cells. The eosinophil percentage and IL-4 in BAL, OVA specific IgE in serum in OVA group were all increased obviously compared with those in saline group (P<0.01). CpG-ODNs could partially relieve the above changes in OVA group (P<0.05). Furthermore, mice treated with CpG-ODNs had slightly increased IFN-γ and IL-10 in BAL, suggesting that Th1 and Treg cytokines might be responsible for the protective role of CpG-ODNs. However, GpC-ODNs did not affect OVA-induced pathological or immunological changes (P>0.05). Conclusion: Our results indicate that CpG-ODNs have therapeutic effects on chronic asthmatic airway remodeling by inducing immuno-resistance mediated by T cells and elevating Th1-to-Treg cytokines.