scholarly journals Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo

2021 ◽  
Author(s):  
Jae-Won Lee ◽  
Mun-Ock Kim ◽  
Yu Na Song ◽  
Jae-Hong Min ◽  
Seong-Man Kim ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Mucus Secretion ◽  
Compound K ◽  
Pkc Signaling

scholarly journals Curcumin Attenuates Asthmatic Airway Inflammation and Mucus Hypersecretion Involving a PPARγ-Dependent NF-κB Signaling Pathway In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tao Zhu ◽  
Zhihong Chen ◽  
Guihua Chen ◽  
Daoxin Wang ◽  
Shuo Tang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Binding Activity ◽  
Mucus Secretion ◽  
Mucus Hypersecretion ◽  
Asthmatic Airway ◽  
Dna Binding Activity

Asthma is characterized by airway inflammation and mucus hypersecretion. Curcumin possessed a potent anti-inflammatory property involved in the PPARγ-dependent NF-κB signaling pathway. Then, the aim of the current study was to explore the value of curcumin in asthmatic airway inflammation and mucus secretion and its underlying mechanism. In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce chronic asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were obtained. MCP-1, MUC5AC, and PPARγ expression and the phosphorylation of NF-κB p65 and NF-κB p65 DNA-binding activity were measured in both the lungs and BEAS-2B cells. shRNA-PPARγ was used to knock down PPARγ expression. We found that OVA-induced airway inflammation and mucus hypersecretion in mice, OVA and IL-4-induced upregulation of MCP-1 and MUC5AC, suppression of PPARγ, and activation and translocation of NF-κB p65 were notably improved by curcumin both in vivo and in vitro. Our data also showed that these effects of curcumin were significantly abrogated by shRNA-PPARγ. Taken together, our results indicate that curcumin attenuated OVA-induced airway inflammation and mucus hypersecretion in mice and suppressed OVA- and IL-4-induced upregulation of MCP-1 and MUC5AC both in vivo and in vitro, most likely through a PPARγ-dependent NF-κB signaling pathway.

Secretory phospholipases A2 stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea

2007 ◽  
Vol 292 (1) ◽  
pp. L62-L67 ◽  
Author(s):  
Kosuke Okamoto ◽  
Jung-Soo Kim ◽  
Bruce K. Rubin
Keyword(s):  
Airway Inflammation ◽  
Neutrophil Elastase ◽  
Lavage Fluid ◽  
Water Soluble ◽  
Mucus Secretion ◽  
Human Neutrophil Elastase ◽  
Lipoxygenase Inhibitor ◽  
Phospholipases A2

Secretory phospholipases A2 (sPLA2) are increased in the bronchoalveolar lavage fluid of patients with asthma and acute respiratory distress syndrome. Intratracheal sPLA2 instillation induces acute lung injury in the rat and guinea pig. We hypothesized that sPLA2 would stimulate mucus secretion in vitro and that intratracheal sPLA2 exposure would induce mucus hypersecretion and airway inflammation in the ferret trachea in vivo. In vitro, porcine pancreatic sPLA2 at a concentration of 0.5 or 5 U/ml significantly increased mucous glycoconjugate (MG) secretion from the excised ferret trachea. P-bromophenacylbromide (a sPLA2 inhibitor), quercetin (a lipoxygenase inhibitor), or MK-886 (a 5-lipoxygenase inhibitor), each at 10−4 M, significantly reduced sPLA2-induced MG secretion. sPLA2-stimulated MG secretion was decreased in Ca2+-free medium. In vivo, ferrets were intubated for 30 min once per day for 3 days using an ETT coated with 20 units of porcine pancreatic sPLA2 mixed in water-soluble jelly. Constitutive MG secretion increased 1 day after sPLA2 exposure and returned to control 5 days later. Human neutrophil elastase (HNE) at 10−8 M increased MG secretion in the sPLA2-exposed trachea compared with that in the control trachea, but methacholine at 10−7 M did not. sPLA2-induced secretory hyperresponsiveness continued for at least 5 days after sPLA2 exposure ended. sPLA2 increased tracheal inflammation, MG secretion, and secretory hyperresponsiveness to HNE probably through enzymatic action rather than by activation of its receptor.

scholarly journals What Have In Vitro Co-Culture Models Taught Us about the Contribution of Epithelial-Mesenchymal Interactions to Airway Inflammation and Remodeling in Asthma?

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1694
Author(s):  
Emmanuel Twumasi Osei ◽  
Steven Booth ◽  
Tillie-Louise Hackett
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Airway Inflammation ◽  
Airway Epithelial ◽  
Disease Pathogenesis ◽  
3 Dimensional ◽  
Lung Epithelial ◽  
Culture Models

As the lung develops, epithelial-mesenchymal crosstalk is essential for the developmental processes that drive cell proliferation, differentiation, and extracellular matrix (ECM) production within the lung epithelial-mesenchymal trophic unit (EMTU). In asthma, a number of the lung EMTU developmental signals have been associated with airway inflammation and remodeling, which has led to the hypothesis that aberrant activation of the asthmatic EMTU may lead to disease pathogenesis. Monoculture studies have aided in the understanding of the altered phenotype of airway epithelial and mesenchymal cells and their contribution to the pathogenesis of asthma. However, 3-dimensional (3D) co-culture models are needed to enable the study of epithelial-mesenchymal crosstalk in the setting of the in vivo environment. In this review, we summarize studies using 3D co-culture models to assess how defective epithelial-mesenchymal communication contributes to chronic airway inflammation and remodeling within the asthmatic EMTU.

Regulation of intestinal goblet cell secretion. III. Isolated intestinal epithelium

1984 ◽  
Vol 247 (6) ◽  
pp. G674-G681 ◽  
Author(s):  
T. E. Phillips ◽  
T. H. Phillips ◽  
M. R. Neutra
Keyword(s):  
Intestinal Epithelium ◽  
Direct Action ◽  
Intercellular Junctions ◽  
Goblet Cells ◽  
Mucus Secretion ◽  
Cell Secretion ◽  
Adult Rats ◽  
Compound Exocytosis

Cholinergic secretagogues evoke mucus secretion from goblet cells in the crypts of small and large intestinal mucosa in vivo and in organ culture. It was not known whether this response reflected a direct action on epithelial cell receptors or an indirect effect involving intermediate neurons of the enteric nervous system. To resolve this, carbachol was applied to isolated intestinal epithelium maintained in vitro. Intact sheets of epithelium, measuring 10–200 mm2, were isolated from the ileum and colon of adult rats following short intravascular perfusion with 30 mM EDTA. The isolated epithelia lacked a basal lamina and cytoplasmic blebs formed on the basal cell surfaces, but cell ultrastructure was normal and intercellular junctions were intact. Autoradiography revealed that both goblet and columnar cells continued to incorporate [3H]glucosamine into nascent secretory macromolecules for at least 45 min after isolation. When exposed to 20 microM carbachol for 5 min, crypt goblet cells discharged their stored mucin granules by compound exocytosis, whereas goblet cells in portions of the epithelium derived from villi or mucosal surfaces were unresponsive. We conclude that cholinergic secretagogues act directly on crypt epithelial cells to elicit mucus secretion.

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.

Effect of Compound K, a Metabolite of Ginseng Saponin, Combined with γ-Ray Radiation in Human Lung Cancer Cells in Vitro and in Vivo

2009 ◽  
Vol 57 (13) ◽  
pp. 5777-5782 ◽  
Author(s):  
Sungwook Chae ◽  
Kyoung Ah Kang ◽  
Weon Young Chang ◽  
Min Jung Kim ◽  
Su Jae Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Compound K ◽  
Ginseng Saponin ◽  
Human Lung Cancer Cells ◽  
Γ Ray

scholarly journals An in Vitro and in Vivo Study of the Effect of Dexamethasone on Immunoinhibitory Function of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

2018 ◽  
Vol 27 (9) ◽  
pp. 1340-1351 ◽  
Author(s):  
Dan Wang ◽  
Yue-Qi Sun ◽  
Wen-Xiang Gao ◽  
Xing-Liang Fan ◽  
Jian-Bo Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Airway Inflammation ◽  
Pluripotent Stem Cell ◽  
Allergic Airway Inflammation ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent ◽  
Immunomodulatory Function

Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) represent a promising cell source for patient-specific cell therapy. We previously demonstrated that they display an immunomodulatory effect on allergic airway inflammation. Glucocorticoids are powerful anti-inflammatory compounds and widely used in the therapy of allergic diseases. However, the effect of glucocorticoids on the immunomodulatory function of iPSC-MSCs remains unknown. This study aimed to determine the effect of dexamethasone (Dex) on the immunomodulatory function of iPSC-MSCs in vitro and in vivo. A total of three human iPSC-MSC clones were generated from amniocyte-derived iPSCs. Anti-CD3/CD28-induced peripheral blood mononuclear cell (PBMC) proliferation was used to assess the effect of Dex on the immunoinhibitory function of iPSC-MSCs in vitro. Mouse models of contact hypersensitivity (CHS) and allergic airway inflammation were induced, and the levels of inflammation in mice were analyzed with the treatments of iPSC-MSCs and Dex, alone and combined. The results showed that Dex did not interfere with the immunoinhibitory effect of iPSC-MSCs on PBMC proliferation. In CHS mice, simultaneous treatment with Dex did not affect the effect of iPSC-MSCs on the inflammation, both in regional draining lymph nodes and in inflamed ear tissue. In addition, co-administration of iPSC-MSCs with Dex decreased the local expression of interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the ears of CHS mice. In the mouse model of allergic airway inflammation, iPSC-MSC treatment combined with Dex resulted in a similar extent of reduction in pulmonary inflammation as iPSC-MSCs or Dex treatment alone. In conclusion, Dex does not significantly affect the immunomodulatory function of iPSC-MSCs both in vitro and in vivo. These findings may have implications when iPSC-MSCs and glucocorticoids are co-administered.

A role for transient receptor potential ankyrin 1 cation channel (TRPA1) in airway hyper-responsiveness?

2015 ◽  
Vol 93 (3) ◽  
pp. 171-176 ◽  
Author(s):  
Aruni Jha ◽  
Pawan Sharma ◽  
Vidyanand Anaparti ◽  
Min H. Ryu ◽  
Andrew J. Halayko
Keyword(s):  
Airway Inflammation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Chronic Obstructive ◽  
Airway Narrowing ◽  
Airway Caliber ◽  
Transient Receptor

Airway smooth muscle (ASM) contraction controls the airway caliber. Airway narrowing is exaggerated in obstructive lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). The mechanism by which ASM tone is dysregulated in disease is not clearly understood. Recent research on ion channels, particularly transient receptor potential cation channel, subfamily A, member 1 (TRPA1), is uncovering new understanding of altered airway function. TRPA1, a member of the TRP channel superfamily, is a chemo-sensitive cation channel that can be activated by a variety of external and internal stimuli, leading to the influx of Ca2+. Functional TRPA1 channels have been identified in neuronal and non-neuronal tissues of the lung, including ASM. In the airways, these channels can regulate the release of mediators that are markers of airway inflammation in asthma and COPD. For, example, TRPA1 controls cigarette-smoke-induced inflammatory mediator release and Ca2+ mobilization in vitro and in vivo, a response tied to disease pathology in COPD. Recent work has revealed that pharmacological or genetic inhibition of TRPA1 inhibits the allergen-induced airway inflammation in vitro and airway hyper-responsiveness (AHR) in vivo. Collectively, it appears that TRPA1 channels may be determinants of ASM contractility and local inflammation control, positioning them as part of novel mechanisms that control (patho)physiological function of airways and ASM.

Nedocromil sodium and airway inflammation in vivo and in vitro☆☆☆★

1996 ◽  
Vol 98 (5) ◽  
pp. S51-S57 ◽  
Author(s):  
Jagdish L. Devalia ◽  
Csaba Rusznak ◽  
Muntasir M. Abdelaziz ◽  
Robert J. Davies
Keyword(s):  
Airway Inflammation ◽  
Nedocromil Sodium

scholarly journals Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Fang Zhang ◽  
Gang Huang ◽  
Bo Hu ◽  
Li-Ping Fang ◽  
E-Hong Cao ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Airway Inflammation ◽  
High Mobility ◽  
Neutralizing Antibody ◽  
Th17 Response ◽  
Neutrophilic Inflammation ◽  
Allergic Lung Inflammation ◽  
Hmgb1 Expression

We demonstrate that high mobility group box 1 protein (HMGB1) directs Th17 skewing by regulating dendritic cell (DC) function. First, ourin vitrostudies reveal that recombinant HMGB1 (rHMGB1) activates myeloid DCs to produce IL-23in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretionin vivoby using a murine model of neutrophilic asthma induced by ovalbumin (OVA) plus lipopolysaccharide (LPS). Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.

Sign in / Sign up

Export Citation Format

Share Document