Immunomodulatory Effects of CpG Oligodeoxynucleotides on House Dust Mite-Induced Airway Inflammation in Mice

Hirose, Izumi; Tanaka, Hiroyuki; Takahashi, Go; Wakahara, Keiko; Tamari, Mayumi; Sakamoto, Tatsuo; Kojima, Seiji; Inagaki, Nobuya; Nagai, Hiroichi

doi:10.1159/000128581

Cited by 14 publications

(16 citation statements)

References 81 publications

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“…It may be necessary to develop another late asthmatic model that can be developed by intratracheal administration of an antigen at a low dose for the long term. In addition, in order to further mimic the pathogenesis, natural antigen contaminated with endotoxin is also indispensable for an ideal model of experimental asthma, as indicated by the literature (34,35).…”

Section: Effects Of Anti-il-5 Mab On the Development Of Airway Remodementioning

confidence: 99%

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

Nabe¹,

Morishita²,

Matsuya³

et al. 2011

J Pharmacol Sci

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Abstract. It is known that the late asthmatic response (LAR), a characteristic feature of asthma, is closely associated with CD4 + Th2 cell-mediated allergic inflammation. Airway remodeling is also a pathogenesis of asthma, but literature reporting roles of CD4 + cells in the remodeling is controversial. There has been no study that simultaneously assessed the roles of CD4 + cells in both LAR and airway remodeling. Sensitized mice were intratracheally challenged with ovalbumin 4 times. Treatment with an anti-CD4 monoclonal antibody (mAb) before the 1st challenge almost completely abolished increase in CD4 + cells in the tissues after the 4th challenge. The late phase increase in airway resistance after the 4th challenge was also completely inhibited by anti-CD4 mAb. Parameters of airway remodeling, subepithelial fibrosis and epithelial thickening were attenuated by treatment, whereas the inhibition was only 30% -40%. Bronchial smooth muscle thickening was not affected. Because interleukin (IL)-5 production as well as eosinophilia was effectively suppressed by anti-CD4 mAb, the effect of anti-IL-5 mAb was also examined, resulting in no inhibition of airway remodeling. Collectively, although the LAR was completely dependent on CD4 + cell activation, airway remodeling was only partially dependent on the cell.

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Section: Effects Of Anti-il-5 Mab On the Development Of Airway Remodementioning

confidence: 99%

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

Nabe¹,

Morishita²,

Matsuya³

et al. 2011

J Pharmacol Sci

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“…Recently, we (17,18) have established a mouse model for allergic asthma using a major allergen, Der f. This mouse model is characterized by eosinophil infiltrates into the airways, increases in the level of interleukin (IL)-13, decrease in the level of interferon-γ (IFN-γ ) in the bronchoalveolar lavage fluid (BALF), AHR to acetylcholine (ACh), and increases in the serum allergenspecific immunoglobulin (Ig) G1 level by repetitive intratracheal administration of the allergen without a T helper type 2 (Th2)-skewing adjuvant. Furthermore, airway remodeling, characterized by severe goblet cell hyperplasia/hypertrophy, subepithelial fibrosis, and increases in the level of TGF-β 1 in the BALF were also demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

et al. 2010

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Abstract. Recent research has focused on the effects of ambient particulate pollution and much evidence has indicated that particulate pollution is associated with the onset of asthma and allergy; however, the effect of diesel exhaust particles (DEP) on the development of allergen-induced airway remodeling has not been fully investigated in vivo. In the present study, we examined the effects of DEP on Dermatophagoides farinae allergens (Der f)-induced asthma-like phenotypes in mice. Mice were administered i.t. 8 times with Der f. DEP were injected i.t. with Der f 4 times throughout the experiment or twice at the sensitization period. In both cases, DEP aggravated Der f-induced increases in airway responsiveness to acetylcholine, the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), serum Der f-specific IgG1 levels, Th2 cytokines and transforming growth factor-β 1 levels in BALF, and amount of hydroxyproline in the right lungs. Furthermore, goblet cell hyperplasia and subepithelial fibrosis were also markedly aggravated. These findings indicate that DEP can potentiate airway remodeling induced by repeated allergen challenge as well as Th2-drived airway hyperresponsiveness, eosinophilic inflammation, and IgG1 production and that DEP can exhibit adjuvant activity for airway remodeling, probably due to the enhancement of allergen sensitization and/or of Th2 polarizing pathways.

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“…52 No recent study for allergic diseases CpG ODNs/i.t. 53 and i.n. 61 CpG ODNs for atopic asthma (RDPC*)/i.h.…”

Section: Probioticsmentioning

confidence: 99%

“…CpG ODNs contain unmethylated CpG motifs, which confer the immunostimulatory properties of bacterial DNA through the ability to induce immune responses. 53,54 CpG ODNs can enhance Th1 immune responses, 55,56 suppress Th2 responses 57,58 and induce regulatory T cells. 59,60 These findings suggest that CpG ODNs can be a therapeutic approach for the treatment of Th2-mediated allergic asthma.…”

Section: Antigen Dose and Formulationmentioning

confidence: 99%

“…The immunomodulatory effects of CpG ODNs on the development of HDM Dermatophagoides farinae (Der f)-induced airway inflammation and remodeling in mice have been reported. 53 Simultaneous intratracheal instillation of CpG ODNs with Der f at the first allergen exposure showed significant inhibition of inflammation in a dose-dependent manner of CpG. For intranasal therapy, Ramaprakash et al found that intranasal CpG therapy attenuated experimental fungal asthma in both a TLR9-dependent and an independent manner.…”

Section: Antigen Dose and Formulationmentioning

confidence: 99%

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Strategies of mucosal immunotherapy for allergic diseases

Chuang

Chiang

2011

Cell Mol Immunol

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Incidences of allergic disease have recently increased worldwide. Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases. Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT), there remains a risk of severe and sometimes fatal anaphylaxis. Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile. This study reviews recent progress in mucosal immunotherapy for allergic diseases. Administration routes, antigen quality and quantity, and adjuvants used are major considerations in this field. Also, direct uses of unique probiotics, or specific cytokines, have been discussed. Furthermore, some researchers have reported new therapeutic ideas that combine two or more strategies. The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation, which includes continuous searching for efficient adjuvants, collecting more information about dominant T-cell epitopes of allergens, and having the proper combination of each. In clinics, when compared to other mucosal routes, sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration, although local and systemic side effects have been reported. Additionally, not every allergen has the same beneficial effect. Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults. Data collected from large, well-designed, double-blind, placebo-controlled, and randomized trials, with post-treatment follow-up, can provide robust substantiation of current evidence.

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Immunomodulatory Effects of CpG Oligodeoxynucleotides on House Dust Mite-Induced Airway Inflammation in Mice

Cited by 14 publications

References 81 publications

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

Complete Dependence on CD4+ Cells in Late Asthmatic Response, but Limited Contribution of the Cells to Airway Remodeling in Sensitized Mice

Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

Strategies of mucosal immunotherapy for allergic diseases

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