Suppression of Allergic Response by CpG Motif Oligodeoxynucleotide–House-Dust Mite Conjugate in Animal Model of Allergic Rhinitis

Mo, Ji‐Hun; Park, Seok-Won; Rhee, Chae‐Seo; Takabayashi, Kenji; Lee, Seung Sin; Quan, Songhua; Kim, In-Sang; Min, Il Yang-Gi; Lee, Chul Hee

doi:10.1177/194589240602000219

Cited by 32 publications

(20 citation statements)

References 33 publications

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“…Once CpG was chemically linked to Amb a 1, it caused a marked increase in IFN-γ level and a shift in the antibody profile from a Th2-directed IgG1 response to a Th1-directed IgG2a response in a murine model of asthma [15]. Similarly, treatment of mitesensitized mice with CpG ODN/Der f conjugate caused a marked increase in IFN-γ levels and decrease of IL-5 level in nasal lavage fluid [28]. Since IFN-γ and IL-12 are both typical Th1 cytokines, reduction of CpG ODNinduced IL-12 release from mast cells by Per a 7 seems disagreed with the above findings.…”

Section: Discussionmentioning

confidence: 99%

Cockroach Allergen per a 7 Down-Regulates Expression of Toll-Like Receptor 9 and IL-12 Release from P815 Cells Through PI3K and MAPK Signaling Pathways

Yang

Xue²,

Wei³

et al. 2012

Cell Physiol Biochem

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Background: As a major source of indoor allergens, cockroach causes perennial rhinitis and asthma. Recently, cockroach feces were reported to contain TLR2 agonist, which could directly activate neutrophils to release cytokines. CpG oligodeoxynucleotide (ODN), a Toll-like receptor (TLR)9 activator was also found to induce proinflammatory cytokine release from mast cells. However, influence of specific cockroach allergen on Th1 cytokine release and expression of TLR9 in mast cells remains uninvestigated. Methods: To investigate effects of Per a 7 on TLR expression and cytokine release from mast cells and their cell signaling mechanisms, P815 cells were challenged by recombinant Per a 7 (rPer a 7), and expression of TLR9 mRNA and protein was assessed mainly by real time PCR and flow cytometry analysis. Detection of phosphorylation of cell signaling components was performed with Western blotting technique. Results: The results showed that rPer a 7 induced up to 72 and 46% down-regulation of expression of TLR9 mRNA and protein, respectively following 16 h incubation period. It induced also approximately 41.1% reduction of IL-12 release. When PD98059, U0126 and LY294002 were pre-incubated with the cells for 30 min they diminished rPer a 7 induced reduction of TLR9 expression and IL-12 release, indicating these events are via activation of ERK and PI3K/Akt signaling pathways. Conclusion: Reduction of IL-12 production and expression of TLR9 in P815 mastocytoma cells by Per a 7 suggests that this major cockroach allergen might contribute to the development of cockroach allergy.

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Section: Discussionmentioning

confidence: 99%

Cockroach Allergen per a 7 Down-Regulates Expression of Toll-Like Receptor 9 and IL-12 Release from P815 Cells Through PI3K and MAPK Signaling Pathways

Yang

Xue²,

Wei³

et al. 2012

Cell Physiol Biochem

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“…Recombinant allergens, naturally occurring allergen isoforms, and allergen-derived peptides are currently being developed and require further analysis in controlled trials [62]. Novel approaches to conventional SLIT or SCIT with mites include: purified [63] and recombinant allergens [64], immunization with DNA-encoding allergens [65,66], the use of adjuvants [67], immunostimulatory sequences or CpG motifs [68], peptides [69,70], or the use of plants as vectors for the delivery of allergens [71]. The use of recombinant allergens, which show very low specific IgE-binding capacity but contain T cellstimulating sequences, holds promise.…”

Section: Novel Approaches To Mite Immunotherapymentioning

confidence: 99%

Mite immunotherapy

Fernández-Caldas¹,

Iraola²,

Boquete³

et al. 2006

Curr Allergy Asthma Rep

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Dermatophagoides pteronyssinus and D. farinae are the most common house dust mites and are among the most common sources of indoor allergens worldwide. These species are very common in humid regions, where most allergic individuals are sensitized to house dust mites. Specific immunotherapy with mite extracts has demonstrated clinical benefits in several double-blind, placebo-controlled trials that are included in recent reviews of subcutaneous immunotherapy, including pediatric and adult patients with rhinoconjunctivitis and or asthma. Most successful studies of mite immunotherapy have used native allergen extracts adsorbed onto aluminum hydroxide, or chemically modified mite-allergen extracts. Several studies have also shown efficacy using sublingual immunotherapy in pediatric and adult patients with asthma and/or rhinitis. Additionally, the efficacy of subcutaneous immunotherapy has been demonstrated in patients with atopic dermatitis, although more double-blind, placebo-controlled studies are needed. Based on several studies, it cannot be concluded that mite immunotherapy is more dangerous or safer than immunotherapy with grasses, epithelia, or animal epithelia. Because the delivery of high doses of allergen carries with it the risk for immunoglobulin E (IgE)-mediated events, several methods have been developed to reduce specific IgE binding to mite-allergen extracts. An important challenge for future mite immunotherapy modalities is the delivery of relatively high doses without a significant risk for severe reactions.

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“…It is an agonist to Toll-like receptor-9 which activates DCs and B cells to produce Th1-specific cytokines and suppresses Th2-modulated allergic responses (21). Co-administration of CpG-containing immunostimulatory oligodeoxynucleotide (ISS-ODN) with HDM allergen has been shown to decrease eosinophilia and IL-5 production while increasing the production of IFN-γ in nasal lavage fluid (25). In the same study, these responses were significantly improved when ISS-ODN was chemically conjugated with HDM allergen.…”

Section: Introductionmentioning

confidence: 99%

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Joshi

Adamcakova‐Dodd

Jing

et al. 2014

AAPS J

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Abstract. Poly(lactic-co-glycolic acid) (PLGA) particles carrying antigen and adjuvant is a promising vaccine system which has been shown to stimulate systemic antigen-specific immune responses. In this study, we investigated the relationship of (i) the sizes of PLGA particle and (ii) the presence of cytosinephosphate-guanine motifs (CpG), with the extent and type of immune response stimulated against Dermatophagoides pteronyssinus-2 (Der p2) antigen. Different sizes of PLGA particles encapsulating CpG were prepared using a double emulsion solvent evaporation method. Mice were vaccinated with Der p2 and different sizes of empty or CpG-loaded PLGA particles. Vaccinated mice were exposed to daily intranasal instillation of Der p2 for 10 days followed by euthanization to estimate leukocyte accumulation in bronchoalveolar lavage (BAL) fluids, antibody profiles, and airway hyperresponsiveness. PLGA particles showed a size-dependent decrease in the proportion of eosinophils found in BAL fluids. Mice vaccinated with the Der p2 coated on 9-μm-sized empty PLGA particles showed increased levels of IgE and IgG1 antibodies as well as increased airway hyperresponsiveness. All sizes of PLGA particles encapsulating CpG prevented airway hyperresponsiveness after Der p2 exposures. Inflammatory responses to Der p2 exposure were significantly reduced when smaller PLGA particles were used for vaccination. In addition, encapsulating CpG in PLGA particles increased IgG2a secretion. This study shows that the size of PLGA particles used for vaccination plays a major role in the prevention of house dust mite-induced allergy and that incorporation of CpG into the PLGA particles preferentially develops a Th1-type immune response.

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Suppression of Allergic Response by CpG Motif Oligodeoxynucleotide–House-Dust Mite Conjugate in Animal Model of Allergic Rhinitis

Cited by 32 publications

References 33 publications

Cockroach Allergen per a 7 Down-Regulates Expression of Toll-Like Receptor 9 and IL-12 Release from P815 Cells Through PI3K and MAPK Signaling Pathways

Cockroach Allergen per a 7 Down-Regulates Expression of Toll-Like Receptor 9 and IL-12 Release from P815 Cells Through PI3K and MAPK Signaling Pathways

Mite immunotherapy

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

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