Toll-like Receptor Expression on Peripheral Blood Mononuclear Cells in Asthmatics; Implications for Asthma Management

Chun, Eunyoung; Lee, So Hee; Lee, Sooyeon; Shim, Eun-Jin; Cho, Sang Heon; Min, Kyung-Up; Kim, You-Young; Park, Heung-Woo

doi:10.1007/s10875-009-9363-z

Cited by 28 publications

(23 citation statements)

References 22 publications

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“…In severe asthma, allergen challenge only increased the expression of Tlr2 and allergen sensitization and challenge significantly increased Tlr1 expression when compared to sensitized only mice. These results are supported by data from animal and human studies which have shown that Tlr2/Tlr1 heterodimers can play both pro- and anti-inflammatory roles in allergic asthma [16, 35]. Interestingly, allergen sensitization and challenge decreased Tlr3 expression in both models.…”

Section: Discussionsupporting

confidence: 62%

Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma

Sagar

Verheijden

Georgiou

et al. 2013

Mediators of Inflammation

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This study aimed at exploring innate and adaptive immunity in allergic asthma by investigation of mRNA expression of pattern recognition receptors, T-cell-specific cytokines, and transcription factors. Mouse models for mild and severe asthma, with similar pathological characteristics observed in humans, were used to study the involved inflammatory markers as a first step in the development of phenotype-directed treatment approaches. In the mild model, mice were sensitized to ovalbumin-Imject Alum and challenged with ovalbumin. In the severe model, mice were sensitized to trinitrophenyl-conjugated ovalbumin and challenged with trinitrophenyl-ovalbumin/IgE immune complex. Pulmonary airway inflammation and mRNA expression of Toll-like receptors (TLRs), NOD-like receptors (NLRs), T cell cytokines, and transcription factors in lung tissue were examined. Different mRNA expression profiles of TLRs, NLRs, T cell cytokines, and transcription factors were observed. In the mild model, Il10 showed the largest increase in expression, whereas in the severe model, it was Inf γ with the largest increase. Expression of Tbet was also significantly increased in the severe model. Inflammation and immunity are differentially regulated in mild and severe experimental asthma. This preclinical data may help in directing clinical research towards a better understanding and therapy in mild and severe asthmatic patients.

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Section: Discussionsupporting

confidence: 62%

Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma

Sagar

Verheijden

Georgiou

et al. 2013

Mediators of Inflammation

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“…Chun and colleagues (19) recently profiled TLR protein expression on peripheral blood mononuclear cells in asthmatics and observed that, unlike TLR1, TLR2, and TLR9, TLR6 expression was significantly lower in asthmatic patients compared with controls. Moreover, this receptor has been associated with decreased susceptibility for the development of atopic asthma (16).…”

Section: Resultsmentioning

confidence: 99%

The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A

Moreira¹,

Cavassani²,

Ismailoglu³

et al. 2011

J. Clin. Invest.

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TLRs are a family of receptors that mediate immune system pathogen recognition. In the respiratory system, TLR activation has both beneficial and deleterious effects in asthma. For example, clinical data indicate that TLR6 activation exerts protective effects in asthma. Here, we explored the mechanism or mechanisms through which TLR6 mediates this effect using mouse models of Aspergillus fumigatus-induced and house dust mite antigen-induced (HDM antigen-induced) chronic asthma. Tlr6 -/-mice with fungal-or HDM antigen-induced asthma exhibited substantially increased airway hyperresponsiveness, inflammation, and remodeling compared with WT asthmatic groups. Surprisingly, whole-lung levels of IL-23 and IL-17 were markedly lower in Tlr6 -/-versus WT asthmatic mice. Tlr6 -/-DCs generated less IL-23 upon activation with lipopolysaccharide, zymosan, or curdlan. Impaired IL-23 generation in Tlr6 -/-mice also corresponded with lower levels of expression of the pathogen-recognition receptor dectin-1 and expansion of Th17 cells both in vivo and in vitro.

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“…TLRs activate transcription factors that increase expression of a variety of inflammatory markers (35). Although TLRs are most often associated with infectious diseases, they have more recently been associated with noninfectious conditions such as asthma (36), inflammatory bowel disease (37), rheumatoid arthritis (38), and T1D. There are 12 known TLRs with various specificities; TLR2 and TLR4 have been implicated in T1D.…”

Section: Tlrsmentioning

confidence: 99%

Toll-like receptors, the NLRP3 inflammasome, and interleukin-1β in the development and progression of type 1 diabetes

2012

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Traditionally, type 1 diabetes (T1D) has been thought of as a disease of cellular immunity, but there is increasing evidence that components of the innate immune system, controlled largely by Toll-like receptors (TLRs), play a significant role in T1D development. TLRs are pattern-recognition molecules on immune cells that recognize pathogens, leading to the production of cytokines such as interleukin-1β (IL1β, encoded by the IL1B gene). IL1β is increased in patients with newly diagnosed T1D and likely acts as an early inflammatory signal in T1D development. Because hyperglycemia is a hallmark of T1D, the effects of hyperglycemia on IL1β expression in peripheral blood mononuclear cells (PBMcs) and islet cells have been examined, but with inconsistent results, and the mechanisms leading to this increase remain unknown. Fatty acids stimulate IL1β expression and may promote inflammation, causing hyperglycemia and insulin resistance. The mechanisms by which IL1β is involved in T1D pathogenesis are controversial. Overall, studies in pancreatic β-cells suggest that IL1β-mediated damage to islet cells involves multiple downstream targets. Potential therapies to decrease the progression of T1D based on IL1β biology include pioglitazone, glyburide, IL1 receptor antagonists, and agents that remove IL1β from the circulation.

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Toll-like Receptor Expression on Peripheral Blood Mononuclear Cells in Asthmatics; Implications for Asthma Management

Abstract: TLR-mediated inflammatory signals contribute to the development and severity of asthma and are not reduced by glucocorticoid treatment, which suggests that a TLR-specific antagonist and glucocorticoid are required for the effective control of airway inflammation in asthmatics.

Cited by 28 publications

References 22 publications

Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma

Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma

The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A

Toll-like receptors, the NLRP3 inflammasome, and interleukin-1β in the development and progression of type 1 diabetes

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