scholarly journals MicroRNA-21 Promotes Allergic Airway Inflammation and AHR and Inhibits Mesenchymal Stem Cell Migration in Cockroach Allergen Induced Asthma Model

2021 ◽  
Author(s):  
Tianli Cheng ◽  
jianfu heng ◽  
Quanhui Mei ◽  
Lijun Chen ◽  
Feng Zeng
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity ◽  
Negative Regulator ◽  
Mouse Bone Marrow ◽  
Asthma Model ◽  
Gene Assay

Abstract BackgroundMesenchymal stem cells (MSCs) have been used to treat asthma in a mouse model. However, the efficacy and mechanism of MSCs are not elucidated. MicroRNAs (miRNAs) play a key rolein asthma and related to the aim of this study was to illustrate the role of miR21 and its influence on MSC migration in asthma model. MethodsA mouse model of asthma was established using cockroach extract (CRE), and miR-21 expression was examined. A miR-21 lentivirus construct was used to investigate the role of miR-21 in vivo and in vitro in mouse bone marrow-derived (BM-) MSCs. A TOPFlash reporter gene assay was used to study the signaling downstream of miR-21. IL-4, IL-5, IL-13, IgE, and IgG1 levels in bronchoalveolar lavage fluids were determined by enzyme-linked immunosorbent assays.ResultsMiR-21 was upregulated in CRE-induced asthmatic mice. MiR-21 promoted allergic airway inflammation and airway hyperreactivity by inhibiting BM-MSC migration. β-Catenin was found to act downstream of miR-21 as a negative regulator of miR-21. Rescue experiments verified that miR-21 inhibited BM-MSC migration by suppressing Wnt/β-catenin signaling.ConclusionMiR-21 promotes allergic airway inflammation and AHR and inhibits BM-MSC migration through Wnt/β-catenin signaling, which may serve as an effective therapeutic target for asthma.

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.

Inhaled Carbenoxolone Prevents Allergic Airway Inflammation and Airway Hyperreactivity in a Mouse Model of Asthma

2008 ◽  
Vol 149 (1) ◽  
pp. 38-46 ◽  
Author(s):  
Arjun Ram ◽  
Shashi Kant Singh ◽  
Vijay Pal Singh ◽  
Sarvesh Kumar ◽  
Balaram Ghosh
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity

Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma

1998 ◽  
Vol 28 (10) ◽  
pp. 3240-3251 ◽  
Author(s):  
Armin Braun ◽  
Elena Appel ◽  
Rina Baruch ◽  
Udo Herz ◽  
Vladimir Botchkarev ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Nerve Growth

scholarly journals Proteomic Analysis of Anti-inflammatory Effects of a Kampo (Japanese Herbal) Medicine “Shoseiryuto (Xiao-Qing-Long-Tang)” on Airway Inflammation in a Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Takayuki Nagai ◽  
Marino Nakao ◽  
Yuliko Shimizu ◽  
Yoshio Kodera ◽  
Masamichi Oh-Ishi ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Mouse Model ◽  
Airway Inflammation ◽  
Bronchial Asthma ◽  
Antibody Titer ◽  
Lung Tissue ◽  
Proteomic Analysis ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity ◽  
Japanese Herbal Medicine

Effects of a Kampo (Japanese herbal) medicine “shoseiryuto (SST, xiao-qing-long-tang in Chinese)”, which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g kg−1 day−1from day 1 to 6 after OVA inhalation, SST reduced the inflammation in lung tissue, the number of eosinophils and the OVA-specific immunoglobulin E (IgE) antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. SST also reduced the airway hyperreactivity at 6 days after the OVA inhalation. Proteomic analysis with the agarose two-dimensional electrophoresis showed that the expression of spectrin α2 was reduced in the lung tissue of OVA-sensitized mice and SST recovered the expression. Western blot and immunohistochemical analyses of lung tissue also confirmed this result. When prednisolone was orally administered at 3 mg kg−1 day−1from day 1 to 6 after OVA inhalation, the inflammation in lung tissue, the number of eosinophils in BAL fluids and airway hyperreactivity were reduced in the OVA-sensitized mice. However, prednisolone did not reduce the OVA-specific IgE antibody titer in BAL fluids and did not recover the expression of spectrin α2 in lung tissue. These results suggest that at least a part of action mechanism of SST against OVA-sensitized allergic airway inflammation in a mouse model is different from that of prednisolone.

scholarly journals Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms

2019 ◽  
Vol 12 (597) ◽  
pp. eaax3332 ◽  
Author(s):  
Brenal K. Singh ◽  
Wen Lu ◽  
Amanda M. Schmidt Paustian ◽  
Moyar Q. Ge ◽  
Cynthia J. Koziol-White ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Asthma ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
Airway Disease ◽  
Negative Regulator ◽  
Airway Smooth Muscle Cells ◽  
T Helper 2

Asthma is a chronic allergic inflammatory airway disease caused by aberrant immune responses to inhaled allergens, which leads to airway hyperresponsiveness (AHR) to contractile stimuli and airway obstruction. Blocking T helper 2 (TH2) differentiation represents a viable therapeutic strategy for allergic asthma, and strong TCR-mediated ERK activation blocks TH2 differentiation. Here, we report that targeting diacylglycerol (DAG) kinase zeta (DGKζ), a negative regulator of DAG-mediated cell signaling, protected against allergic asthma by simultaneously reducing airway inflammation and AHR though independent mechanisms. Targeted deletion of DGKζ in T cells decreased type 2 inflammation without reducing AHR. In contrast, loss of DGKζ in airway smooth muscle cells decreased AHR but not airway inflammation. T cell–specific enhancement of ERK signaling was only sufficient to limit type 2 airway inflammation, not AHR. Pharmacological inhibition of DGK diminished both airway inflammation and AHR in mice and also reduced bronchoconstriction of human airway samples in vitro. These data suggest that DGK is a previously unrecognized therapeutic target for asthma and reveal that the inflammatory and AHR components of asthma are not as interdependent as generally believed.

scholarly journals Importance of group X–secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model

2007 ◽  
Vol 204 (4) ◽  
pp. 865-877 ◽  
Author(s):  
William R. Henderson ◽  
Emil Y. Chi ◽  
James G. Bollinger ◽  
Ying-tzang Tien ◽  
Xin Ye ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Asthma Model ◽  
Acid Metabolites ◽  
Cytosolic Pla2 ◽  
Subepithelial Fibrosis ◽  
Goblet Cell Metaplasia

Arachidonic acid metabolites, the eicosanoids, are key mediators of allergen-induced airway inflammation and remodeling in asthma. The availability of free arachidonate in cells for subsequent eicosanoid biosynthesis is controlled by phospholipase A2s (PLA2s), most notably cytosolic PLA2-α. 10 secreted PLA2s (sPLA2s) have also been identified, but their function in eicosanoid generation is poorly understood. We investigated the role of group X sPLA2 (sPLA2-X), the sPLA2 with the highest in vitro cellular phospholipolysis activity, in acute and chronic mouse asthma models in vivo. The lungs of sPLA2-X−/− mice, compared with those of sPLA2-X+/+ littermates, had significant reduction in ovalbumin-induced infiltration by CD4+ and CD8+ T cells and eosinophils, goblet cell metaplasia, smooth muscle cell layer thickening, subepithelial fibrosis, and levels of T helper type 2 cell cytokines and eicosanoids. These data direct attention to sPLA2-X as a novel therapeutic target for asthma.

Resistin-like molecule-β is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung

2007 ◽  
Vol 293 (2) ◽  
pp. L305-L313 ◽  
Author(s):  
Anil Mishra ◽  
Meiqin Wang ◽  
James Schlotman ◽  
Nikolaos M. Nikolaidis ◽  
Charles W. DeBrosse ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Goblet Cell ◽  
Allergic Airway Inflammation ◽  
Mouse Lung ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Leukocyte Accumulation

Resistin-like molecule (RELM)-β is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM-β has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM-β is strongly induced by diverse allergens and T helper type 2 (Th2) cytokines by an IL-13- and STAT6-dependent mechanism. To understand the in vivo role of RELM-β, we delivered recombinant murine RELM-β intratracheally to naïve mice. RELM-β induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM-β was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM-β had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM-β had fibroblast motogenic activity. These results identify RELM-β as a Th2-associated cytokine with potent inflammatory and remodeling activity.

scholarly journals Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

2020 ◽  
Vol 8 (12) ◽  
pp. 1878
Author(s):  
Qingyu Wu ◽  
Ilka Jorde ◽  
Olivia Kershaw ◽  
Andreas Jeron ◽  
Dunja Bruder ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Influenza A Virus ◽  
Influenza A ◽  
Inflammatory Responses ◽  
Morphological Changes ◽  
Acute Infection ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity ◽  
Sublethal Dose

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4+ and CD8+ lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI.

Fecal Microbiota Transplantation (FMT) Alleviates Ovalbumin-induced Allergic Airway Inflammation in Neonatal Mice via the PD-1/PD-L1 Axis

2021 ◽  
Author(s):  
Cheng Wu ◽  
Juan Zhang ◽  
Yuan-Yuan Jia ◽  
Xing-Zhi Wang ◽  
Qiu-hong Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Airway Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Allergic Airway Inflammation ◽  
Fecal Microbiota ◽  
Cell Death Protein

Abstract Asthma is the common respiratory disorder in children, which is associated with abnormal gut microbiota. Fecal microbiota transplantation (FMT) has successfully ameliorated the symptoms of several diseases and restored the balance of gut microbiota. However, there are few researches about the role of FMT in asthma. This study aimed at exploring whether FMT can alleviate allergic airway inflammation in neonatal mice and elucidating the probable underlying mechanism. A neonatal mouse model of ovalbumin (OVA)-induced allergic asthma was established and transplanted with fecal filtrates. Our results manifested that FMT could protect against the allergic airway inflammation through enhancing mesenteric CD11c + CD103 + DCs and accumulating mucosal Helios + Tregs. Besides, the programmed cell death protein 1/programmed cell death protein 1 ligand (PD-1/PD-L1) signal pathway was inhibited after FMT intervention. Furthermore, this beneficial role of FMT was also associated with the rebalanced gut microbiota, such as Akkermansia. Thus, our findings indicated that FMT intervention could exert a therapeutic effect in a neonatal mouse model of OVA-induced allergic airway inflammation through its remodeling on gut microbiota and regulation of Treg homeostasis via the PD-1/PD-L1 axis, which might be used as an alternative therapy for allergic asthma.

scholarly journals Interleukin-22 attenuates allergic airway inflammation in ovalbumin-induced asthma mouse model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingru Wang ◽  
Shengnan Gao ◽  
Jingyuan Zhang ◽  
Chunxiao Li ◽  
Hongwen Li ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Interleukin 22 ◽  
Asthma Model ◽  
Asthma Mouse Model

Abstract Background Allergic asthma is a chronic airway inflammatory disease with a number of cytokines participating in its pathogenesis and progress. Interleukin (IL)-22, which is derived from lymphocytes, acts on epithelial cells and play a role in the chronic airway inflammation. However, the actual role of IL-22 in allergic asthma is still unclear. Therefore, we explored the effect of IL-22 on allergic airway inflammation and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)-induced asthma mouse model. Methods To evaluate the effect of IL-22 in an allergic asthma model, BALB/c mice were sensitized and challenged with OVA; then the recombinant mouse IL-22 was administered intranasally 24 h prior to each challenge. The IL-22 levels in lung homogenates and bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay, respectively. AHR was evaluated through indicators including airways resistance (Rrs), elastance (Ers) and compliance (Crs); the inflammatory cell infiltration was assessed by quantification of differential cells counts in BALF and lung tissues stained by hematoxylin and eosin (H&E); IL-22 specific receptors were determined by immunohistochemistry staining. Results The concentration of IL-22 was significantly elevated in the OVA-induced mice compared with the control mice in lung homogenates and BALF. In the OVA-induced mouse model, IL-22 administration could significantly attenuate AHR, including Rrs, Ers and Crs, decrease the proportion of eosinophils in BALF and reduce inflammatory cell infiltration around bronchi and their concomitant vessels, compared with the OVA-induced group. In addition, the expression of IL-22RA1 and IL-10RB in the lung tissues of OVA-induced mice was significantly increased compared with the control mice, while it was dramatically decreased after the treatment with IL-22, but not completely attenuated in the IL-22-treated mice when compared with the control mice. Conclusion Interleukin-22 could play a protective role in an OVA-induced asthma model, by suppressing the inflammatory cell infiltration around bronchi and their concomitant vessels and airway hyperresponsiveness, which might associate with the expression of its heterodimer receptors. Thus, IL-22 administration might be an effective strategy to attenuate allergic airway inflammation.

Sign in / Sign up

Export Citation Format

Share Document