title: Treatment of allergic rhinitis with CpG oligodeoxynucleotides alleviates the lower airway outcomes of combined allergic rhinitis and asthma syndrome via a mechanism that possibly involves in TSLP.
abstract: Thymic stromal lymphopoietin (TSLP) is a critical regulator of immune responses associated with Th2 cytokine-mediated inflammation. Intranasal administration of oligodeoxynucleotides with CpG motifs (CpG-ODNs) might improve lower airway outcomes of combined allergic rhinitis and asthma syndrome (CARAS), but the inherent mechanisms of CpG-ODNs are not well defined. This study investigated whether CpG-ODNs treated to upper airway could reduce lower airway TSLP expression as well as whether this reduction could contribute to the alleviation of lower allergic inflammation and airway hyper-reactivity (AHR) in CARAS mice.
  
  
  
  Ovalbumin (OVA)-sensitized BALB/c mice were intranasal OVA exposure three times a week for 3 weeks. CpG-ODNs or an anti-TSLP mAb was administered to a subset of these mice 1 hour after intranasal OVA challenge, followed by 5 days of OVA aerosol challenge. The resulting immunological variables, nasal symptoms, and nasal mucosa and lung tissues pathology were evaluated. TSLP production in the lung tissues and bronchoalveolar lavage fluid (BALF) were determined by RT-PCR, western blotting or enzyme-linked immunosorbent assay.
  
  
  
  The CARAS mice exhibited overexpression of TSLP in the lung tissues and BALF, and also demonstrated significant increases in BALF and splenocyte Th2-associated cytokine production, serum OVA-specific IgE, nose and lung pathologies, and AHR. Intranasal administration of CpG-ODNs restored TSLP in the lower airway, and it significantly reduced the following parameters: Th2-type cytokine production levels; the percentage of eosinophils in the BALF; IL-4 and IL-5 concentrations in the supernatants of cultured splenic lymphocytes; serum OVA-specific IgE; peribronchial inflammation score in the lungs; and nose pathology and nasal symptoms. Similar results were obtained when the CARAS mice were treated with an anti-TSLP mAb to block intranasal TSLP activity.
  
  
  
  Treatment with intranasal CpG-ODNs improves lower airway immunological variable outcomes in the CARAS model via a mechanism that possibly involves in suppressing pulmonary TSLP-triggered allergic inflammation.
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Li
authors.affiliation: b Department of Pediatrics , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Zhuang-Gui
authors.initials: ZG
authors.lastname: Chen
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: c Department of Otolaryngology, Head and Neck Surgery , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zou
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Hai-Ling
authors.initials: HL
authors.lastname: Yang
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Ping
authors.initials: P
authors.lastname: Meng
authors.affiliation: a Department of Pulmonary Diseases , Institute of Respiratory Diseases of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Tian-Tuo
authors.initials: TT
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D065631:Rhinitis, Allergic / Q000188:drug therapy* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: CpG oligodeoxynucleotides; allergic rhinitis; asthma; cytokines; thymic stromal lymphopoietin