Effect of intranasal treatment with Toll-like receptor 9 ligand CpG oli-godeoxynucleotides on airway inflammation in mice with allergic com-bined airway disease / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the therapeutic effect of intranasal administration of CpG oligodeoxynucleotides (CpG-ODN), compared with intradermal administration, on lower airway inflammation in ovalbumin (OVA)-induced al-lergic combined airway disease (ACAD) mouse model.METHODS: Totally 30 female BALB/c mice aged from 6 to 8 weeks were randomly divided into control group , allergic rhinitis model group (AR group), ACAD group, ACAD intrana-sally treated with CpG-ODN group (CpG i.n.group) and ACAD intradermally treated with CpG-ODN group (CpG i.d. group).The mice were sensitized and challenged with OVA .Treatment with CpG-ODN was also performed during chal-lenge, either intranasally or intradermally .Immunologic variables and nasal symptom were studied .RESULTS:Compared with CpG i.d.group and ACAD group, the percentage of eosinophils from bronchoalveolar lavage fluid (BALF), the levels of Th2 cytokine production in BALF and supernatants of cultured splenic lymphocytes , OVA-specific IgE from blood , peri-bronchial inflammation score in the lung , and nasal symptoms were significantly reduced in CpG i .n.group.CONCLU-SION:Allergic rhinitis treated by CpG-ODN has a significant improvement on lower airway inflammation in ACAD mouse model;and it may be more effective when administrated intranasally than intradermally .

Role of TLR9 in pathogenesis of glomerulonephritis / 吉林大学学报(医学版)

Objective To investigate the role of TLR9 in the glomerulonephritis through observing the changes of Toll-like receptor 9 in the glomerulo nephritis kidney tissue with or without CpG-ODN stimulation .Methods Wistar male rats were randomly divided into normal group(N),nephritis model group(M),CpG-ODN group(CpG) and GpC-ODN group(GpC).The urine samples were collected at 2,4,6 and 8 weeks after treatment,respectively.Blood samples were collected at the end of the last urine sample was collected,and the kidney tissue was collected,then the rats were killed.24 h urine protein was measured by Coomassie light blue technique.Serum album and renal function were determined by serological method.The pathologic changes of kidney were observed by light microscope and NF-?B p65 expression was detected using immunohistochemystry,RT-PCR was performed to detect the expressions of TLR9,INF-? and IL-6 mRNA.Results The expression of TLR9 was lighter in group M,and significantly increased after CpG-ODN stimulation compared with group M.Furthermore,24 h urine protein excretion was markedly increased,serum album was markedly decreased.The histopathologic changes of kidney were more severe.The mesangial cells(MCs) proliferated diffusifully in midrange and wide range,some of the glomeruli formatted cellularity crescent,micrangium loop was limitted,mononuclear macrophile cells were seen in the mesangial region.Conclusion Inflammatory factors mediated by TLR9 can deteriorate the biochemical and histopathologic changes.The immunologic reaction mediated by TLR9 is one of the mechanisms for the glomerulonephtitis' progression.

Effects of CpG-oligodeoxynucleotides in Chronic Inflammation and Remodeling of Airway in a Murine Model of Bronchial Asthma / 결핵및호흡기질환

BACKGROUND: Airway remodeling of the asthmatic airway, the result of persistent inflammation in the bronchial wall, is associated with irreversible airway obstruction and the severity of asthma. Previous reports had represented that adminitering CpG-oligodeoxynucleotides (CpG-ODN) before sensitization or challenge by allergens inhibits the development of eosinophilic airway inflammation in a murine model of asthma, but the effects of CpG-ODNs on chronic inflammation and airway remodeling had not been characterized. To investigate the influence of CpG-ODNs on chronic inflammation and remodeling of the airway, we performed studies using a murine model of chronic allergen-induced asthma. METHODS: Balb/C mice were sensitized to ovalbumin(OVA) and subsequently exposed to nebulized OVA by means of inhalation twice weekly for 7 weeks. CpG-ODNs(30 microgram) was administered intraperitoneally at sensitization. After final inhalation, mice were evaluated for airway hyperresponsiveness, chronic airway inflammation and remodeling. RESULTS: The mice exposed to chronic and recurrent airway challenge with OVA had persistent airway hyperresponsiveness, chronic inflammation and airway remodeling. Mice treated with CpG-ODNs exhibited decreased bronchial hyperresponsiveness, OVA-specific IgE, chronic inflammation and evidence of airway remodeling, including goblet cell hyperplasia and subepithelial fibrosis. CONCLUSION: CpG-ODNs was thought to prevent chronic inflammation and remodeling changes in a murine model of chronic asthma.

Effect of CpG Oligodeoxynucleotides on Airways of Mice with Established Airways Inflammation

PURPOSE: Airways eosinophilia and increased IgE, characteristic features of asthma, result from a predominant Th2 response. In this study, we investigated the effect of CpG oligodeoxynucleotides (ODNs) on the inhibition of airways eosinophilia in mice with established airway inflammation. We also investigated the immunological mechanisms involved. METHODS: Groups of BALB/c mice were sensitized intradermally with ovalbumin(OVA). At week 10, airway inflammation was induced by intranasal challenge of the mice with OVA. At week 14, the mice were challenged intranasally again with OVA in the presence and without the presence of CpG ODNs. Mice with saline administration served as negative controls. Bronchoalveolar lavage fluids(BALF) were obtained and eosinophils were counted. Th1 and Th2 cytokines in the spleen cell cultures were measured by ELISA. Serum OVA-specific IgE and IgG2a antibodies were also measured by ELISA. RESULTS: BALF eosinophils were significantly inhibited in the CpG ODNs-treated mice(P<0.01). IgE and IgG2a levels increased significantly in both CpG ODNs-treated and untreated groups as compared to the negative control group; there was, however, no significant difference between the two groups four days after intranasal administration of CpG ODNs. Cytokine analysis revealed decreased production of IL-4, IL-5, and IL-13 and increased production of IL-12 in the CpG ODNs-treated group as compared to the untreated group. Interestingly, IFN-gamma levels were not upregulated in the CpG ODNs-treated group. CONCLUSION: CpG ODNs vaccination is a potentially useful approach for reversing airways eosinophilia in mice with established airways inflammation.

Effects of Immunostimulatory CpG-Oligodeoxynucleotides of Bronchial Asthma in Rat / 결핵

BACKGROUND AND OBJECT: Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the TH1-type immune response and down-regulate the TH2-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperrestponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. MATERIALS AND METHODS: 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovallbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl)on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-(TH1-type cytokine) and IL-4(TH2-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. RESULTS: In the BALF of the CpG group, the IFN-γ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5Ac gene expression was observed between the CpG group and the Ac group. CONCLUSION: ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the TH1-type immune response with the down-regulation of the TH2-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

Effect of CpG oligodeoxynucleotides on antigen induced allergic airway reaction in mice / 第二军医大学学报

Objective: To investigate the effect of CpG motif oligodeoxynucleotides (CpG ODN) on the antigen induced allergic airway reaction in mice. Methods: The asthma model was set up in the C57BL/6 mice with OVA, the CpG ODN in the dose of 30 ?g was co administered intraperitoneally with the antigen in sensitization stage to study its effect on the airway allergenic reactions. Results: (1)Compared with the control, coadministration of CpG ODN in sensitization phase significantly inhibited airway eosinophilia after antigen challenge( P