scholarly journals A20-binding inhibitor of NF-κB (ABIN) 2 negatively regulates allergic airway inflammation

2018 ◽  
Vol 215 (11) ◽  
pp. 2737-2747 ◽  
Author(s):  
Sonia Ventura ◽  
Florencia Cano ◽  
Yashaswini Kannan ◽  
Felix Breyer ◽  
Michael J. Pattison ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Drug Target ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Negative Regulator ◽  
Disease Models ◽  
Wild Type ◽  
Dust Mite ◽  
Airway Responses ◽  
Deficient Mice

TPL-2 MAP 3-kinase promotes inflammation in numerous mouse disease models and is an attractive anti-inflammatory drug target. However, TPL-2–deficient (Map3k8−/−) mice develop exacerbated allergic airway inflammation to house dust mite (HDM) compared with wild type controls. Here, we show that Map3k8D270A/D270A mice expressing kinase dead TPL-2 had an unaltered response to HDM, indicating that the severe airway inflammation observed in Map3k8−/− mice is not due to blockade of TPL-2 signaling and rather reflects a TPL-2 adaptor function. Severe allergic inflammation in TPL-2–deficient mice was likely due to reduced levels of ABIN-2 (TNIP2), whose stability depends on TPL-2 expression. Tnip2E256K knock-in mutation, which reduced ABIN-2 binding to A20, augmented the HDM-induced airway inflammation, but did not affect TPL-2 expression or signaling. These results identify ABIN-2 as a novel negative regulator of allergic airway responses and importantly indicate that TPL-2 inhibitors would not have unwanted allergic comorbidities.

scholarly journals CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
C. López-Pacheco ◽  
G. Soldevila ◽  
G. Du Pont ◽  
R. Hernández-Pando ◽  
E. A. García-Zepeda
Keyword(s):  
Airway Inflammation ◽  
Chemokine Receptors ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment ◽  
First Time ◽  
Early Phases ◽  
Deficient Mice

Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma.

scholarly journals Allergin-1 Immunoreceptor Suppresses House Dust Mite–Induced Allergic Airway Inflammation

2020 ◽  
Vol 204 (4) ◽  
pp. 753-762 ◽  
Author(s):  
Haruka Miki ◽  
Satoko Tahara-Hanaoka ◽  
Mariana Silva Almeida ◽  
Kaori Hitomi ◽  
Shohei Shibagaki ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
House Dust ◽  
House Dust Mite ◽  
Allergic Airway Inflammation ◽  
Dust Mite

Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness

2015 ◽  
Vol 309 (8) ◽  
pp. L789-L800 ◽  
Author(s):  
Akihiko Taniguchi ◽  
Nobuaki Miyahara ◽  
Koichi Waseda ◽  
Etsuko Kurimoto ◽  
Utako Fujii ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Group 2 ◽  
Airway Responses

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE−/− mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

scholarly journals Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness

2013 ◽  
Vol 9 (1) ◽  
pp. 21 ◽  
Author(s):  
Hsu-Chung Liu ◽  
Shun-Yuan Pai ◽  
Winston TK Cheng ◽  
Hsiao-Ling Chen ◽  
Tung-Chou Tsai ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Mite Allergen ◽  
Dust Mite ◽  
Dust Mite Allergen

scholarly journals IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite–induced asthma models

2017 ◽  
Vol 214 (10) ◽  
pp. 3037-3050 ◽  
Author(s):  
Takashi Ito ◽  
Koichi Hirose ◽  
Aiko Saku ◽  
Kenta Kono ◽  
Hiroaki Takatori ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
House Dust ◽  
House Dust Mite ◽  
Cytokine Production ◽  
Allergic Airway Inflammation ◽  
Lung Epithelial Cells ◽  
Intratracheal Administration ◽  
Lung Epithelial ◽  
Dust Mite

Previous studies have shown that IL-22, one of the Th17 cell–related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway inflammation and Th2 and Th17 cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative allergen, were exacerbated in IL-22-deficient mice. We also found that IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway inflammation and Th2 cytokine induction. Moreover, exostatin-like 3 (EXTL3), a functional Reg3γ binding protein, is expressed in lung epithelial cells, and intratracheal administration of recombinant Reg3γ suppresses HDM-induced thymic stromal lymphopoietin and IL-33 expression and accumulation of type 2 innate lymphoid cells in the lung. Collectively, these results suggest that IL-22 induces Reg3γ production from lung epithelial cells and inhibits the development of HDM-induced allergic airway inflammation, possibly by inhibiting cytokine production from lung epithelial cells.

scholarly journals HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice

2019 ◽  
Vol 316 (1) ◽  
pp. L269-L279 ◽  
Author(s):  
Tianwen Lai ◽  
Mindan Wu ◽  
Chao Zhang ◽  
Luanqing Che ◽  
Feng Xu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cytokines ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Protective Role ◽  
In Vivo Models

Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/− mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/− mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation.

scholarly journals β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Go Kato ◽  
Koichiro Takahashi ◽  
Hiroki Tashiro ◽  
Keigo Kurata ◽  
Hideharu Shirai ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Airway Inflammation ◽  
House Dust ◽  
House Dust Mite ◽  
Allergic Airway Inflammation ◽  
Adrenergic Agonist ◽  
Dust Mite
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