Toll-Like Receptor-9 Agonist Inhibits Airway Inflammation, Remodeling and Hyperreactivity in Mice Exposed to Chronic Environmental Tobacco Smoke and Allergen

Song, Dae Jin; Min, Myung Goo; Miller, Marina; Cho, Jae Youn; Yum, Hye Yung; Broide, David H.

doi:10.1159/000250437

Cited by 17 publications

(13 citation statements)

References 81 publications

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“…Some data suggest that Toll-like receptor expression and function in cigarette smoking are causally linked to COX and NADPH activation, oxidative stress, and damage, 60 whereas other results show that the activation of Toll-like receptor-9 by stimulation with an agonist reduces lung inflammation in response to secondhand smoke. 61 Several experimental studies demonstrated that, apart from causing vascular endothelial dysfunction, cigarette smoke causes physical damage to the vascular endothelium (Figure). In essence, 2 forms of damage were observed: (1) contraction of endothelial cells, mediated by oxidation and collapse of the tubulin system, which is reversible and may be part of the clinical symptoms of smoking-caused reduction of FMD, 57 and (2) endothelial cell death.…”

Section: Arterioscler Thromb Vasc Biol March 2014mentioning

confidence: 99%

Smoking and Cardiovascular Disease

Meßner

Bernhard

2014

ATVB

841

329

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Abstract-Smoking represents one of the most important preventable risk factors for the development of atherosclerosis. The present review aims at providing a comprehensive summary of published data from clinical and animal studies, as well as results of basic research on the proatherogenic effect of smoking. Extensive search and review of literature revealed a vast amount of data on the influence of cigarette smoke and its constituents on early atherogenesis, particularly on endothelial cells. Vascular dysfunction induced by smoking is initiated by reduced nitric oxide (NO) bioavailability and further by the increased expression of adhesion molecules and subsequent endothelial dysfunction. Smoking-induced increased adherence of platelets and macrophages provokes the development of a procoagulant and inflammatory environment. After transendothelial migration and activation, macrophages take up oxidized lipoproteins arising from oxidative modifications and transdifferentiate into foam cells. In addition to direct physical damage to endothelial cells, smoking induces tissue remodeling, and prothrombotic processes together with activation of systemic inflammatory signals, all of which contribute to atherogenic vessel wall changes. There are still great gaps in our knowledge about the effects of smoking on cardiovascular disease. However, we know that smoking cessation is the most effective measure for reversing damage that has already occurred and preventing fatal cardiovascular outcomes. Clinical DataEvidence for smoking-induced initial vascular damage and endothelial dysfunction stems from an array of clinical studies analyzing endothelial function using various techniques. 6 As mentioned above, in 1993, Celermajer et al 5 were able to show that continuous smoking impairs FMD of the brachial artery in a dose-dependent manner, shown by the strong association between FMD and pack years smoked. This was also found to be the case with coronary arteries in a study by Zeiher et al. 7 Interestingly, reduction of endothelium-dependent dilatation by smoking was reversible, and significant improvement of FMD 1 year after cessation has been reported. 8 Likewise, a recent study of Amato et al 9 revealed that smoking light cigarettes impairs FMD as much as smoking regular cigarettes, arguing against light cigarettes as a less harmful alternative.Measurement of FMD represents a useful tool to assess the effects of smoking on the vascular wall. Independent of its FMD reducing activity, smoking was shown to induce other proatherogenic alterations in the vascular wall (eg, by deposition of smoke chemicals). The time needed to restore interrupted functions of the vascular endothelium will depend on the specific process that has caused the endothelial damage; some alterations of the endothelial wall may vanish more rapidly than others, without these being reflected by improved FMD.Clinical studies assessing the interrelation of secondhand smoking and FMD reported strong correlations. Secondhand smoking was shown to impair endo...

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Section: Arterioscler Thromb Vasc Biol March 2014mentioning

confidence: 99%

Smoking and Cardiovascular Disease

Meßner

Bernhard

2014

ATVB

841

329

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“…Recent publications in mice have shown that tCS exposure can on the one hand enhance allergic sensitization and the allergic pulmonary Th2 response [15][16][17][18][19]. Recent publications in mice have shown that tCS exposure can on the one hand enhance allergic sensitization and the allergic pulmonary Th2 response [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Effects of conventional tobacco smoke and nicotine‐free cigarette smoke on airway inflammation, airway remodelling and lung function in a triple allergen model of severe asthma

Tilp

Bucher

Haas

et al. 2016

Clin Experimental Allergy

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Our experiments show that tCS exposure reduces allergen-induced Th2 response in the lung and associated collagen I production and development of airway hyperreactivity. With the exception on collagen I formation, these effects were not dependent on Toll-like receptor 4. The observed anti-Th2 effects of both nicotine and nicotine-free herbal cigarette smoke together suggests that tCS reduces the Th2 responses through nicotine and other products released by burning tobacco.

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“…So far, specific allergen immunotherapy (SIT) represents the only ‘etiologic' treatment that directs towards the basis of atopic respiratory disease and influences the natural history of AR and asthma [3]. To develop safer and more efficacious allergy vaccines or novel stand-alone therapeutics, innate immunity stands out as a major target since it is the first line of defense [4,5]. Innate immunity enables initial recognition of invading pathogens and presents them to the immune system to elicit an appropriate adaptive immune response.…”

Section: Introductionmentioning

confidence: 99%

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

Aryan

Holgate

Radzioch

et al. 2014

Int Arch Allergy Immunol

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Toll-like receptors (TLR) belong to a large family of pattern recognition receptors known as the ancient ‘gatekeepers' of the immune system. TLRs are located at the first line of defense against invading pathogens as well as aeroallergens, making them interesting targets to modulate the natural history of respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or prophylactic preparations useful for asthma/allergic rhinitis (AR) patients. MPL® (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9 agonist, show strong immunogenicity effects that make them appropriate adjuvants for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific allergen immunotherapy, currently the only available ‘curative' treatment for respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so far reported with such compounds targeting TLRs, with the most common adverse effects being transient and local irritation (e.g. redness, swelling and pruritus). Many other compounds that target TLRs have been found to suppress airway inflammation, eosinophilia and airway hyper-responsiveness in various animal models of allergic inflammation. Indeed, in the future a wide variability of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are likely to emerge.

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Toll-Like Receptor-9 Agonist Inhibits Airway Inflammation, Remodeling and Hyperreactivity in Mice Exposed to Chronic Environmental Tobacco Smoke and Allergen

Cited by 17 publications

References 81 publications

Smoking and Cardiovascular Disease

Smoking and Cardiovascular Disease

Effects of conventional tobacco smoke and nicotine‐free cigarette smoke on airway inflammation, airway remodelling and lung function in a triple allergen model of severe asthma

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

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