Expression of toll-like receptors 2 and 4 in subjects with asthma by total serum IgE level

Crespo-Lessmann, Astrid; Mateus, Eder; Vidal, Sílvia; Ramos-Barbón, David; Torrejón, Montserrat; Giner, Jordi; Soto-Retes, Lorena; Júarez, Cándido; Plaza, Vicente

doi:10.1186/s12931-016-0355-2

Cited by 20 publications

(10 citation statements)

References 45 publications

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“…The serum total IgE might play a role as a mediator in the development of allergic diseases. The high serum total IgE concentration was associated with the risk for allergic sensitization [33], In addition, high serum total IgE increased macrophage expression of TLR4 in induced sputum in asthmatic subjects [34]. This outcome may result from a link between innate immunity and IgE-mediated adaptive immune responses in asthma.…”

Section: Discussionmentioning

confidence: 99%

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

Gao

Zhang

et al. 2020

Allergy Asthma Clin Immunol

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Background: Allergic rhinitis (AR) is believed to be a complex genetic disease. The last decade has been marked by the publication of more than 20 genome-wide association studies (GWASs) of AR and associated allergic phenotypes and allergic diseases, which have shown allergic diseases and traits to share a large number of genetic susceptibility loci. The aim of present study was therefore to investigate the highly replicated allergy related genes and variants as candidates for AR in Han Chinese subjects. Methods: A total of 762 AR patients and 760 control subjects were recruited, and a total of 58 susceptible variants previously reported to be associated with allergic traits were choose for replication. Results: Logistic regression analyses revealed that in the co-dominant-effect model as assessed by the AIC, compared with wild-type carriers, significant AR risk were associated with rs9865818 in LPP (P = 0.029, OR = 1.469 for GG vs. AA); rs6554809 in DNAH5 (P = 0.000, OR = 1.597 for TC vs. CC); rs1438673 in WDR36-CAMK4 loci (P = 0.037, OR = 1.396 for CC vs.TT), rs7775228 in HLA region (P = 0.000, OR = 1.589 for TC vs.TT), rs7203459 in CLEC16A (P = 0.025, OR = 0.731 for TC vs. TT). Conclusion: We replicated Han Chinese AR-specific susceptibility loci in LPP, DNAH5, HLA, CLEC16A and WDR36-CAMK4. Further understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.

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Section: Discussionmentioning

confidence: 99%

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

Gao

Zhang

et al. 2020

Allergy Asthma Clin Immunol

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“…Asthma is a chronic disorder of the airways associated with episodes of bronchial constriction, mucus production, and immune cell infiltration. The inflammation associated with disease can be driven by allergic or non‐allergic mechanisms, where the activation of Toll‐like receptors (TLRs) on epithelial cells and macrophages regulates the initial nature of the innate inflammatory response . TLR4 activation in response to bacterial components, such as lipopolysaccharide (LPS), will drive nuclear factor (NF)‐κB‐driven inflammatory programming towards IL‐1β, IL‐6, and TNF‐α production in macrophages, promoting the activity of type 1 (M1)‐resident populations and neutrophilic inflammation.…”

Section: Introductionmentioning

confidence: 99%

GSTO1‐1 is an upstream suppressor of M2 macrophage skewing and HIF‐1α‐induced eosinophilic airway inflammation

Sokulsky

Goggins

Sherwin

et al. 2020

Clin Experimental Allergy

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Background: Glutathione S-transferases omega class 1 (GSTO1-1) is a unique member of the GST family regulating cellular redox metabolism and innate immunity through the promotion of LPS/TLR4/NLRP3 signalling in macrophages. House dust mite (HDM) triggers asthma by promoting type 2 responses and allergic inflammation via the TLR4 pathway. Although linked to asthma, the role of GSTO1-1 in facilitating type 2 responses and/or HDM-driven allergic inflammation is unknown. Objective:To determine the role of GSTO1-1 in regulating HDM-induced allergic inflammation in a preclinical model of asthma. Methods:Wild-type and GSTO1-1-deficient mice were sensitized and aeroallergen challenged with HDM to induce allergic inflammation and subsequently hallmark pathophysiological features characterized. Results:By contrast to HDM-challenged WT mice, exposed GSTO1-1-deficient mice had increased numbers of eosinophils and macrophages and elevated levels of eotaxin-1 and -2 in their lungs. M1 macrophage-associated factors, such as IL-1β and IL-6, were decreased in GSTO1-1-deficient mice. Conversely, M2 macrophage factors such as Arg-1 and Ym1 were up-regulated. HIF-1α expression was found to be higher in the absence of GSTO1-1 and correlated with the up-regulation of M2 macrophage markers. Furthermore, HIF-1α was shown to bind and activate the eotaxin-2 promotor. Hypoxic conditions induced significant increases in the levels of eotaxin-1 and -2 in GSTO1-deficient BMDMs, providing a potential link between inflammationinduced hypoxia and the regulation of M2 responses in the lung. Collectively, our results suggest that GSTO1-1 deficiency promotes M2-type responses and increased levels of nuclear HIF-1α, which regulates eotaxin (s)-induced eosinophilia and increased disease severity. Conclusion & Clinical Implication:We propose that GSTO1-1 is a novel negative regulator of TLR4-regulated M2 responses acting as an anti-inflammatory pathway. The discovery of a novel HIF-1α-induced eotaxin pathway identifies an unknown connection between hypoxia and the regulation of the severity of allergic inflammation in asthma. K E Y W O R D S asthma, chemokines, eosinophils, hypoxia, macrophages S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Sokulsky LA, Goggins B, Sherwin S, et al. GSTO1-1 is an upstream suppressor of M2 macrophage skewing and HIF-1α-induced eosinophilic airway inflammation.Clin Exp Allergy. 2020;50:609-624. https://doi.

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“…These studies demonstrated that TLR4 function is likely to be required also in the airway epithelia, which might undermine the barrier function of the epithelium ( 27 , 34 ). Nevertheless, asthmatic subjects with high total serum IgE show increased macrophage expression of TLR4 in induced sputum ( 35 ). Thus, the aim of this study was to investigate the role of TLR4 in asthma-like features such as inflammatory infiltrate, airway hyperreactivity, and mucus exacerbation in mice exposed to S1P.…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 4 Is Essential for the Expression of Sphingosine-1-Phosphate-Dependent Asthma-Like Disease in Mice

et al. 2017

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Sphingosine-1-phosphate (S1P) levels significantly increase in bronchoalveolar lavage (BAL) of asthmatic patients following segmental allergen challenge and this increase well correlates with pulmonary inflammation. Epidemiological, genetic, clinical, and experimental data indicate a potential for the toll-like receptor 4 (TLR4) to initiate and exacerbate allergic airway diseases. The aim of this study was to evaluate the contribution of TLR4 in S1P-dependent asthma-like disease in mice. BALB/c or TLR4 defective (C3H/HeJ) mice received S1P (10 ng/mouse), LPS (0.1 μg/mouse) or S1P + LPS. Furthermore, S1P-treated BALB/c mice were injected with the purified rabbit anti-TLR4 antibody (10 μg/mouse). S1P administration induced airway hyperreactivity and pulmonary inflammation associated to an increase in the percentage of dendritic cells (DCs) and macrophages into the lung of BALB/c mice. These effects were coupled to a reduction of DCs in the mediastinic lymph node. All these S1P-mediated effects were absent in TLR4 defective mice or reversed by treatment with a purified rabbit anti-TLR4 antibody. Confocal analysis of pulmonary sections showed a significant increase in TLR4+ cells and a similar presence of S1P1 and TLR4 following S1P challenge. Accordingly, the immunoprecipitation evidenced an increased S1P1/TLR4 interaction. In conclusion, our findings suggest that a functional interaction between S1P1 and TLR4 leads to an enhanced allergic inflammatory response. Thus, S1P pathway contributes to the sentinel role played by innate immunity providing new targets for prevention and treatment of allergic airway diseases.

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Expression of toll-like receptors 2 and 4 in subjects with asthma by total serum IgE level

Cited by 20 publications

References 45 publications

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

GSTO1‐1 is an upstream suppressor of M2 macrophage skewing and HIF‐1α‐induced eosinophilic airway inflammation

Toll-Like Receptor 4 Is Essential for the Expression of Sphingosine-1-Phosphate-Dependent Asthma-Like Disease in Mice

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