DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation

Qiu, Jing; Li, Guoping; Liu, Zhigang; Ran, Peixing; Zhong, Nanshan

doi:10.1097/00029330-200602010-00002

Cited by 4 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibition of TLRs expression by MAPK inhibitors might directly affect the transcriptional level by inactivation of MAPK‐dependent transcriptional factors; or, these inhibitors could block the production of proinflammatory cytokines and indirectly diminish the inflammatorily induced up‐regulation of TLRs expression. These results also confirm those of in vivo animal studies that have demonstrated airway hyperresponsiveness and elevated intrapulmonary response and cytokine levels in rDer p2‐sensitized C56B/L and Balb/c mice (Tsai et al, 2002; Qiu et al, 2006).…”

Section: Discussionsupporting

confidence: 87%

Der p2 activates airway smooth muscle cells in a TLR2/MyD88‐dependent manner to induce an inflammatory response

Chiou¹,

Lin

2009

Journal Cellular Physiology

View full text Add to dashboard Cite

Der p2 is a major allergen from Dermatophagoides pteronyssinus, the main species of house dust mite and a major inducer of asthma, inducing harmful respiratory inflammatory responses by activating cells in the respiratory tract, leading to an unstable status. We hypothesize that Der p2 may induce local inflammatory responses by directly affecting airway smooth muscle (ASM) cells. In this study, we demonstrated that Der p2 raised nuclear factor-kappa B (NF-kappaB) and extracellular signal-regulated kinase (ERK) 1/2 activation and induced a high level of proinflammatory cytokines expression in primary cultured ASM cells. Der p2 activated the MyD88 signaling pathway through toll-like receptor (TLR) 2, not through TLR4. Notably, Der p2 stimulated ASM cells to increase phosphorylation of ERK1/2 and expression of c-Fos, which were also important in the T helper type 2 (Th2) immune response. These results suggest that Der p2 induces asthma through the MyD88 signaling pathway in respiratory tissue.

show abstract

Section: Discussionsupporting

confidence: 87%

Der p2 activates airway smooth muscle cells in a TLR2/MyD88‐dependent manner to induce an inflammatory response

Chiou¹,

Lin

2009

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…The production of recombinant allergens of common allergens from DNA sequences that can be mutated, fragmented or chimerised leads to efficient hypoallergenic mixtures of allergens for treatment [ 14 , 17 , 18 ]. Additionally important is the ability of producing T cell epitopes without B cell epitopes, which reduces adverse reactions [ 12 , 16 , 17 ] or new technologies like covalently linked T cell epitopes [ 14 ], DNA vaccines encoding allergens [ 19 ], production of fusion proteins to increase allergen presentation [ 20 ], or expression of recombinant allergens in lactic bacteria able to colonise the gut [ 21 ]. Equally promising is the production of random peptide libraries to determine structural equivalents, so called mimotopes [ 14 ], producing shorter peptides [ 16 , 22 ], though patients may develop de novo IgE antibodies against the treatment peptide.…”

Section: Introductionmentioning

confidence: 99%

Treatment of allergic asthma: Modulation of Th2 cells and their responses

et al. 2011

View full text Add to dashboard Cite

Atopic asthma is a chronic inflammatory pulmonary disease characterised by recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell-mediated inflammatory response in the airways. It is currently treated and, more or less, controlled depending on severity, with bronchodilators e.g. long-acting beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs such as corticosteroids (inhaled or oral), leukotriene modifiers, theophyline and anti-IgE therapy. Unfortunately, none of these treatments are curative and some asthmatic patients do not respond to intense anti-inflammatory therapies. Additionally, the use of long-term oral steroids has many undesired side effects. For this reason, novel and more effective drugs are needed. In this review, we focus on the CD4+ Th2 cells and their products as targets for the development of new drugs to add to the current armamentarium as adjuncts or as potential stand-alone treatments for allergic asthma. We argue that in early disease, the reduction or elimination of allergen-specific Th2 cells will reduce the consequences of repeated allergic inflammatory responses such as lung remodelling without causing generalised immunosuppression.

show abstract

“…We reported that a DNA vaccine encoding the whole segment of Derp2 allergen prevents allergic pulmonary inflammation, probably by inhibiting the STAT6 signaling pathway in mice with Derp2 allergen-induced allergic airway inflammation 4 . It was reported that amino acid residues 21-27, 73-78, 118-119 of DerP2 were important allergens for IgE epitopes 5 .…”

Section: Introductionmentioning

confidence: 99%

Derp2-mutant gene vaccine inhibits airway inflammation and up-regulates Toll-like receptor 9 in an allergic asthmatic mouse model

2010

Asian Pac J Allergy Immunol

View full text Add to dashboard Cite

Background: A DNA vaccine encoding the whole segment of the Derp2 allergen could prevent allergic airway inflammation in a Derp2 allergen-induced allergic airway inflammation mouse model. Objective: This study investigated the effect of DNA vaccine encoding Derp2-mutant gene in which an IgE epitope was deleted on airway inflammation and the role of TLR9 in the asthmatic mouse model. Methods: A Derp2-mutant DNA vaccine was constructed. Mice were immunized, sensitized and challenged. Airway inflammation, airway hyper reactivity (AHR) and serum antibody were tested. The expression of Toll like receptor9 (TLR9) was detected with western-blot and immunehistochemistry. Results:We demonstrated that the Derp2-mutant-DNA induced IgG2a and inhibited IgE production, inhibited airway allergenic inflammation and AHR. Derp2-mutant-DNA vaccine induce TLR9 expression in lung tissue. Conclusions:The data indicate that allergen DNA vaccine deleted IgE epitope could prevent allergenic airway inflammation, AHR, and upregulate lung TLR9 express.

show abstract

DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation

Cited by 4 publications

References 18 publications

Der p2 activates airway smooth muscle cells in a TLR2/MyD88‐dependent manner to induce an inflammatory response

Der p2 activates airway smooth muscle cells in a TLR2/MyD88‐dependent manner to induce an inflammatory response

Treatment of allergic asthma: Modulation of Th2 cells and their responses

Derp2-mutant gene vaccine inhibits airway inflammation and up-regulates Toll-like receptor 9 in an allergic asthmatic mouse model

Contact Info

Product

Resources

About