CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma

Jain, Vipul V.; Kitagaki, Kunihiko; Businga, Thomas R.; Hussaın, Iftikhar; George, Caroline; O’Shaughnessy, Patrick T.; Kline, Joel N.

doi:10.1067/mai.2002.129371

Cited by 117 publications

(97 citation statements)

References 30 publications

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“…ISS administration not only prevented the development of these structural features of airway remodeling, but also inhibited the development of airway hyperreactivity, eosinophilic inflammation, airway mucus expression, and reduced levels of profibrotic growth factors including TGF-␤ and IL-13 (13). In this study we have investigated whether ISS can reverse established airway remodeling, as opposed to the previous studies that demonstrated ISS can prevent airway remodeling (13,15). In prior studies examining whether ISS can prevent airway remodeling we started the therapeutic intervention with ISS before the onset of the first of a series of 3 mo of repetitive OVA challenges (13).…”

mentioning

confidence: 79%

“…As peribronchial deposition of type III and type V collagen is a characteristic feature of remodeling in asthma, we were interested to determine whether ISS could not only prevent deposition of collagen as demonstrated in previous studies (12,15), but was also able to reverse the collagen already deposited in the remodeled airway. In this study we demonstrate that ISS can reverse allergen-induced peribronchial collagen deposition of types III and type V collagen by reducing accumulation of peribronchial CD4 ϩ cells that drive ongoing eosinophil and macrophage accumulation, expression of TGF-␤, and collagen deposition.…”

Section: Discussionmentioning

confidence: 99%

“…ISS is as effective as corticosteroids in preventing (1), or reversing (7), eosinophilic inflammation and airway hyperreactivity in mouse models. More recently, studies in our (13) and other laboratories (15) have demonstrated that prophylactic administration of ISS can prevent airway remodeling when administered to mice before starting inhalation challenge with allergen. Prophylactic ISS administration significantly prevents features of airway remodeling including peribronchial fibrosis, as well as the allergen-induced increased thickness of the peribronchial smooth muscle layer (13).…”

mentioning

confidence: 99%

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Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Youn

Miller

Baek

et al. 2004

The Journal of Immunology

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To determine whether immunostimulatory sequences of DNA (ISS) can reverse established airway remodeling, mice that had developed airway remodeling following 3 mo of repetitive OVA challenges, were treated with ISS for 1–3 mo. Systemic administration of ISS to mice that had already developed established airway remodeling significantly reduced the degree of airway collagen deposition (assessed by lung collagen content, peribronchial trichrome staining, and immunostaining with anticollagen type III and type V Abs). ISS reduced bronchoalveolar lavage and lung levels of TGF-β1 and reduced the number of TGF-β1-positive eosinophils and TGF-β1-positive mononuclear cells recruited to the airway. In vitro studies demonstrated that ISS inhibited TGF-β1 expression by macrophages (RAW 264.7 cell line and bone marrow-derived macrophages). In addition, ISS significantly reduces lung levels of expression of the chemokine thymus- and activation-regulated chemokine, as well as the number of peribronchial CD4+ lymphocytes that express Th2 cytokines that promote peribronchial fibrosis. Overall, these studies demonstrate that ISS can reverse features of airway collagen deposition by reducing levels of lung TGF-β1, as well as by reducing levels of the chemokine thymus- and activation-regulated chemokine and the numbers of peribronchial CD4+ lymphocytes that drive the ongoing Th2 immune response.

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mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Youn

Miller

Baek

et al. 2004

The Journal of Immunology

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“…The finding of high TLR9 expression in the present study is particularly interesting because TLR9 is the receptor for bacterial CpG motifs. Numerous studies have shown that CpG can inhibit de novo and established allergic responses in animal and human models [29][30][31]. Therefore, it is logical to speculate that chlamydial infection, via modulation of TLR expression, can change the function of DC, leading to decreased allergen-specific Th2 cell and, to a lesser degree, enhanced Th1 cell development.…”

Section: Discussionmentioning

confidence: 99%

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

et al. 2004

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Our previous study has shown that Chlamydia lung infection can inhibit local eosinophilic inflammation induced by allergen sensitization and challenge, which is correlated with altered cytokine production. In the present study, we examined the role played by dendritic cells (DC) in chlamydial infection-mediated modulation of allergic responses. The results showed that DC freshly isolated from Chlamydia-infected mice (iIDC), unlike those from naive control mice (iNDC), could efficiently modulate immune responses to ovalbumin in vitro and in vivo. Co-culture of freshly isolated DC with naive CD4 cells from T cell receptor transgenic mice (DO11.10) showed that iIDC directed Th1-dominant, while iNDC directed Th2-dominant, allergen-specific CD4 T cell responses. Moreover, adoptive transfer of iIDC, but not iNDC, could inhibit systemic and local eosinophilia induced by allergen exposure. The reduction of eosinophilia was associated with a decrease in IL-5 receptor expression on bone marrow cells and the production of IL-5 and IL-13 by T lymphocytes. Analysis of the DC showed that iIDC expressed significantly higher levels of mRNA for Toll-like receptor 9 and produced more IL-12 compared to iNDC. The data demonstrate a critical role played by DC in infection-mediated inhibition of allergic responses.

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“…To determine whether Bbs mutations predispose mice to airway hyperresponsiveness, as occurs in asthma, we used an ovalbumin immunization protocol (28). Mice were systemically immunized with ovalbumin/alum and then exposed to aerosolized antigen.…”

Section: Bbs-null Mice Do Not Exhibit Increased Airway Hyperresponsivmentioning

confidence: 99%

Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia

Shah

Farmen²,

Moninger³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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107

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Mutations in a group of genes that contribute to ciliary function cause Bardet-Biedl syndrome (BBS). Most studies of BBS have focused on primary, sensory cilia. Here, we asked whether loss of BBS proteins would also affect motile cilia lining the respiratory tract. We found that BBS genes were expressed in human airway epithelia, and BBS2 and BBS4 localized to cellular structures associated with motile cilia. Although BBS proteins were not required for ciliogenesis, their loss caused structural defects in a fraction of cilia covering mouse airway epithelia. The most common abnormality was bulges filled with vesicles near the tips of cilia. We discovered this same misshapen appearance in airway cilia from Bbs1, Bbs2, Bbs4, and Bbs6 mutant mice. The structural abnormalities were accompanied by functional defects; ciliary beat frequency was reduced in Bbs mutant mice. Previous reports suggested BBS might increase the incidence of asthma. However, compared with wild-type controls, neither airway hyperresponsiveness nor inflammation increased in Bbs2 Ϫ/Ϫ or Bbs4 ؊/؊ mice immunized with ovalbumin. Instead, these animals were partially protected from airway hyperresponsiveness. These results emphasize the role of BBS proteins in both the structure and function of motile cilia. They also invite additional scrutiny of motile cilia dysfunction in patients with this disease.asthma ͉ basal body

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CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma

Cited by 117 publications

References 30 publications

Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia

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