Toll-like Receptor 4 Deficiency Aggravates Airway Hyperresponsiveness and Inflammation by Impairing Neutrophil Apoptosis in a Toluene Diisocyanate-Induced Murine Asthma Model

Ailin Tao,Lihong Yao 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions: These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Bearing capacity of H-section beam wrapped with ceramsite concrete

Xuechun Liu,Kun Meng,Ailin Zhang,Tao Zhu,Cheng Yu 국제구조공학회 2021 Steel and Composite Structures, An International J Vol.40 No.5

In this study, an H-section steel beam with circular holes in a web wrapped with ceramsite concrete (SBWCC) was studied. Static load-bearing capacity tests and finite element analysis were performed on two groups of specimens with different sections. The H-section steel and wrapped ceramsite concrete were well bonded. The load-bearing capacity of the SBWCC was 10% larger than that of the pure H-section steel beam without holes in the web, except for its dead weight. The stiffness of the SBWCC was slightly larger than that of the pure H-section steel beam without holes. The wrapped ceramsite concrete avoided the elastic local instability of the steel beam flange and web. Based on the finite element model verified by experiments, the influences of hole diameter, hole spacing, and U-shaped stirrups on the flexural capacity of the specimens were analyzed. The formulas for the load-bearing capacities and short-term stiffness of the SBWCC were proposed and verified by tests and finite element analysis.

Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells

Shan Wang,Meifang He,Linmei Li,Zhihua Liang,Zehong Zou,Ailin Tao 한국유방암학회 2016 Journal of breast cancer Vol.19 No.3

Cell-in-cell structures are created by one living cell entering another homotypic or heterotypic living cell, which usually leads to the death of the internalized cell, specifically through caspase-dependent cell death (emperitosis) or lysosome-dependent cell death (entosis). Although entosis has attracted great attention, its occurrence is controversial, because one cell line used in its study (MCF-7) is deficient in caspase-3. Methods: We investigated this issue using MCF-7 and A431 cell lines, which often display cell-in-cell invasion, and have different levels of caspase-3 expression. Cell-in-cell death morphology, microstructures, and signaling pathways were compared in the two cell lines. Results: Our results confirmed that MCF-7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene. These cells underwent cell death that lacked typical apoptotic properties after staurosporine treatment, whereas caspase-3-sufficient A431 cells displayed typical apoptosis. The presence of caspase-3 was related neither to the lysosome-dependent nor to the caspase-dependent cell-in-cell death pathway. However, the existence of caspase-3 was associated with a switch from lysosome-dependent cell-in-cell death to the apoptotic cell-in-cell death pathway during entosis. Moreover, cellular hypoxia, mitochondrial swelling, release of cytochrome C, and autophagy were observed in internalized cells during entosis. Conclusion: The occurrence of caspase-independent entosis is not a cell-specific process. In addition, entosis actually represents a cellular self-repair system, functioning through autophagy, to degrade damaged mitochondria resulting from cellular hypoxia in cell-in-cell structures. However, sustained autophagy-associated signal activation, without reduction in cellular hypoxia, eventually leads to lysosome-dependent intracellular cell death.

The Importance of Allergen Avoidance in High Risk Infants and Sensitized Patients: A Meta-analysis Study

Wu Huiyan,Guo Yuhe,Wang Juan,Zhang Junyan,Zhang Xiaojun,Tao Ailin 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.6

Purpose: At this time, there is uncertainty regarding whether allergen avoidance is the most appropriate strategy for managing or preventing allergies. The purpose of this study was to evaluate the effectiveness of allergen avoidance in the prevention of allergic symptoms in previously sensitized patients and newborns that have the potential to develop allergies. Methods: We performed online searches of articles published from January 1980 to December 2012 in PubMed and The Cochrane Central Register of Controlled Trials, and selected articles involving randomized controlled trials (RCTs) and allergen avoidance. The parameters used to determine allergenic potential in newborns included the risk ratio (RR) of eczema, asthma, rhinitis, wheeze, and cough. The methods employed to evaluate previously sensitized patients were the standardized mean difference (SMD) of forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR). Data quality was assessed using the Jadad scale. Results: A total of 14 RCTs were identified. Meta-analysis demonstrated that allergen avoidance for newborns did not reduce the subsequent incidence of allergic diseases (eczema, P=0.21; rhinitis, P=0.3; cough, P=0.1) but significantly reduced the incidence of asthma and wheezing in high-risk infants (asthma, P=0.03; wheeze, P=0.0004). However, previously sensitized patients who reduced their exposure to known allergens did not show improvement in their lung functions (FEV1, P=0.3; PEFR morning, P=0.53; PEFR evening, P= 0.2; PEFR, P=0.29). Conclusions: Allergen avoidance may not always be successful in preventing allergic symptoms. However, rigorous methodological studies are required to confirm this hypothesis.

Early IL-17A Prevention Rather Than Late IL-17A Neutralization Attenuates Toluene Diisocyanate-Induced Mixed Granulocytic Asthma

Chen Shuyu,Yu Li,Deng Yao,Liu Yuanyuan,Wang Lingwei,Li Difei,Yang Kai,Liu Shengming,Tao Ailin,Chen Rongchang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.5

Purpose: Interleukin (IL)-17A plays a critical role in the pathogenesis of allergic airway inflammation. Yet, the exact roles of IL-17A in asthma are still controversial. Thus, the aim of this study was to dissect the roles of IL-17A in toluene diisocyanate (TDI)-induced mixed granulocytic asthma and to assess the effects of neutralizing antibody in different effector phases on TDI-induced asthma. Methods: IL-17A functions in allergic airway inflammation were evaluated using mice deficient in IL-17A (Il17a−/−) or IL-17A monoclonal antibody (IL-17A mab, intraperitoneally, 50 μg per mouse, 100 μg per mouse). Moreover, the effects of exogenous recombinant IL (rIL)-17A in vivo (murine rIL-17A, intranasally, 1 μg per mouse) and in vitro (human rIL-17A, 100 ng/mL) were investigated. Results: TDI-induced mixed granulocytic airway inflammation was IL-17A-dependent because airway hyperreactivity, neutrophil and eosinophil infiltration, airway smooth muscle thickness, epithelium injury, dysfunctional T helper (Th) 2 and Th17 responses, granulocytic chemokine production and mucus overproduction were more markedly reduced in the Il17a−/− mice or by IL-17A neutralization during the sensitization phase of wild-type (WT) mice. By contrast, IL-17A neutralization during the antigen-challenge phase aggravated TDI-induced eosinophils recruitment, with markedly elevated Th2 response. In line with this, instillation of rIL-17 during antigen sensitization exacerbated airway inflammation by promoting neutrophils aggregation, while rIL-17A during the antigen-challenge phase protected the mice from TDI-induced airway eosinophilia. Moreover, rIL-17A exerted distinct effects on eosinophil- or neutrophil-related signatures in vitro. Conclusions: Our data demonstrated that IL-17A was required for the initiation of TDI-induced asthma, but functioned as a negative regulator of established allergic inflammation, suggesting that early abrogation of IL-17A signaling, but not late IL-17A neutralization, may prevent the progression of TDI-induced asthma and could be used as a therapeutic strategy for severe asthmatics in clinical settings.

China Consensus Document on Allergy Diagnostics

Chen Hao,Li Jing,Cheng Lei,Gao Zhongshan,Lin Xiaoping,Zhu Rongfei,Yang Lin,Tao Ailin,Hong Haiyu,Tang Wei,Guo Yinshi,Huang Huaiqiu,Sun Jinlyu,Lai He,Lei Cheng,Liu Guanghui,Xiang Li,Chen Zhuanggui,Ma Ha 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.2

The prevalence of allergic diseases has increased dramatically in recent years in China, affecting the quality of life in 40% of the population. The identification of allergens is the key to the diagnosis of allergic diseases. Presently, several methods of allergy diagnostics are available in China, but they have not been standardized. Additionally, cross-sensitization and co-sensitization make allergy diagnostics even more complicated. Based on 4 aspects of allergic disease (mechanism, diagnosis procedures, allergen detection in vivo and in vitro as well as the distribution map of the most important airborne allergens in China) and by referring to the consensus of the European Society of Allergy and Clinical Immunology, the World Allergy Organization, and the important literature on allergy diagnostics in China in recent years, we drafted this consensus of allergy diagnostics with Chinese characteristics. It aims to standardize the diagnostic methods of allergens and provides a reference for health care givers. The current document was prepared by a panel of experts from the main stream of professional allergy associations in China.