scholarly journals Aesculetin Inhibits TLR4 and EGFR-Mediated Airway Mucus Hypersecretion and Thickening Induced by Urban Particulate Matter

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 353-353
Author(s):  
Suyeon Oh ◽  
Young-Hee Kang
Keyword(s):  
Periodic Acid ◽  
Ros Production ◽  
Periodic Acid Schiff ◽  
Mucus Production ◽  
Bronchial Epithelial ◽  
Mucus Hypersecretion ◽  
Funding Sources ◽  
Collagen Accumulation ◽  
Leukocyte Number ◽  
Masson Trichrome Staining

Abstract Objectives uPM10 is microscopic particles of solid or liquid matter suspended in the air. Particulates are the most harmful form of air pollution due to their ability to penetrate deep into the lungs, blood streams and brain, causing diverse health problems. Mucus hypersecretion is a pathological symptom evoked in the bronchi and bronchioles. Excess mucus production can narrow the airways, limit airflow, and accelerate a decline in lung function. Aesculetin, a major component of Sancho tree and Chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. However, its effect on mucus hypersecretion has been poorly understood. Methods Mice were orally administrated with 10 mg/kg aesculetin and exposed to 6 μg/ml uPM10 for 8 weeks. Airway thickening and collagen accumulation were stained with H&E staining and Masson trichrome staining. The ROS production and mucus hypersecretion were examined with DHE staining, Alcian blue, periodic acid schiff staining and Western blotting. Bronchial epithelial BEAS-2B cells were treated 1–20 μM aesculetin, 20 μg/ml OxPAPC, and 1μM Erlotinib with 2 μg/ml uPM10 for 8 h or 48 h. The protein induction of TLR4, EGFR, and MUC5AC were measured. Results Exposure of mice to uPM10 enhanced total leukocyte number in the BALF with increase in neutrophils and lymphocytes, which was reversed by oral administration of 10 mg/kg aesculetin. In addition, aesculetin attenuated airway thickening along with collagen accumulation, mucus hypersecretion and ROS production elevated by uPM10 inhalation. Nontoxic aesculetin at the concentrations of 1–20 μM inhibited the induction of collagen proteins and MUC5AC in BEAS-2B cells promoted by 2 μg/ml uPM10. On the other hand, uPM10 accelerated the induction of TLR4 and EGFR in BEAS-2B cells, which dampened by 20 μM aesculetin. Both receptors inhibitor reduced the MUC5AC induction in BEAS-2B cells stimulated by uPM10. Conclusions These results demonstrate that aesculetin ameliorated airway thickening and mucus hypersecretion caused by uPM10 inhalation. Therefore, aesculetin maybe a promising agent treating progressive respiratory disorders elicited by urban microparticulates. Funding Sources This work was supported by the BK21 FOUR(Fostering Outstanding Universities for Research, 4220200913807) funded by the National Research Foundation of Korea (NRF).

Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia

2004 ◽  
Vol 287 (1) ◽  
pp. L127-L133 ◽  
Author(s):  
Je Hyeong Kim ◽  
Sung Yong Lee ◽  
Sang Myeon Bak ◽  
In Bum Suh ◽  
Sang Yeub Lee ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Bacterial Infections ◽  
Inflammatory Responses ◽  
Periodic Acid ◽  
Growth Factor Receptor ◽  
Sprague Dawley ◽  
Neutrophilic Infiltration ◽  
Periodic Acid Schiff ◽  
Mucus Hypersecretion ◽  
Egfr Expression

Bacterial infections of the lung are known to induce inflammatory responses, which lead to mucus hypersecretion. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and its activation. Furthermore, matrix metalloproteinases (MMPs), especially MMP-9, have been reported to promote the transmigration of activated neutrophils. In this study, we investigated the associations between lipopolysaccharide (LPS)-induced goblet cell (GC) metaplasia and EGFR expression and the effects of MMP inhibitor (MMPI). Various concentrations of LPS were instilled into the tracheas of pathogen-free Sprague-Dawley rats, and airways were examined at different times after LPS instillation. To examine the role of MMP-9, we treated rats 3 days before LPS instillation and daily thereafter with MMPI. Neutrophilic infiltration, Alcian blue/periodic acid-Schiff (AB/PAS) staining, and immunohistochemical staining for MUC5AC, EGFR, and MMP-9 were performed. The instillation of LPS increased AB/PAS and MUC5AC staining in time- and dose-dependent manners, and treatment with MMPI significantly prevented GC metaplasia. The instillation of LPS into the trachea also induced neutrophilic infiltration and EGFR and MMP-9 expression in the airway epithelium, and MMPI was found to significantly prevent neutrophil recruitment, GC metaplasia, and EGFR and MMP-9 expression. This study demonstrates that the MMP-9 and EGFR cascades are associated with LPS-induced mucus hypersecretion.

scholarly journals Necroptosis Contributes to Urban Particulate Matter-Induced Airway Epithelial Injury

2018 ◽  
Vol 46 (2) ◽  
pp. 699-712 ◽  
Author(s):  
Feng Xu ◽  
Man Luo ◽  
Lulu He ◽  
Yuan Cao ◽  
Wen Li ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Pulmonary Inflammation ◽  
Periodic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Periodic Acid Schiff ◽  
Mucus Production ◽  
Gm Csf ◽  
Mucin Expression

Background/Aims: Necroptosis, a form of programmed necrosis, is involved in the pathologic process of several kinds of pulmonary diseases. However, the role of necroptosis in particulate matter (PM)–induced pulmonary injury remains unclear. The objective of this study is to investigate the involvement of necroptosis in the pathogenesis of PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction, both in vitro and in vivo. Methods: PM was administered into human bronchial epithelial (HBE) cells or mouse airways, and the inflammatory response and mucus production were assessed. The mRNA expressions of IL6, IL8 and MUC5AC in HBE cells and Cxcl1, Cxcl2, and Gm-csf in the lung tissues were detected by quantitative real-time RT-PCR. The secreted protein levels of IL6 and IL8 in culture supernatants and Cxcl1, Cxcl2, and Gm-csf in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). We used Western blot to measure the protein expressions of necroptosis-related proteins (RIPK1, RIPK3, and Phospho-MLKL), NF-κB (P65 and PP65), AP-1 (P-c-Jun and P-c-Fos) and MUC5AC. Cell necrosis and mitochondrial ROS were detected using flow cytometry. In addition, pathological changes and scoring of lung tissue samples were monitored using hemoxylin and eosin (H&E), periodic acid-schiff (PAS) and immunohistochemistry staining. Results: Our study showed that PM exposure induced RIP and MLKL-dependent necroptosis in HBE cells and in mouse lungs. Managing the necroptosis inhibitor Necrostatin-1 (Nec-1) and GSK’872, specific molecule inhibitors of necroptosis, markedly reduced PM-induced inflammatory cytokines, e.g., IL6 and IL8, and MUC5AC in HBE cells. Similarly, administering Nec-1 significantly reduced airway inflammation and mucus hyperproduction in PM-exposed mice. Mechanistically, we found PM–induced necroptosis was mediated by mitochondrial reactive oxygen species-dependent early growth response gene 1, which ultimately promoted inflammation and mucin expression through nuclear factor κB and activator protein-1 pathways, respectively. Conclusions: Our results demonstrate that necroptosis is involved in the pathogenesis of PM–induced pulmonary inflammation and mucus hyperproduction, and suggests that it may be a novel target for treatment of airway disorders or disease exacerbations with airborne particulate pollution.

Goblet Cell Density of the Inferior Turbinates in Patients with Perennial Allergic and Nonallergic Rhinitis

1997 ◽  
Vol 11 (3) ◽  
pp. 233-236 ◽  
Author(s):  
Gilead Berger ◽  
Zvi Marom ◽  
Dov Ophir
Keyword(s):  
Goblet Cell ◽  
Periodic Acid ◽  
Inferior Turbinate ◽  
Goblet Cells ◽  
Nonallergic Rhinitis ◽  
Periodic Acid Schiff ◽  
Mucus Production ◽  
The Mean ◽  
Normal Controls ◽  
Goblet Cell Density

Nasal mucus production is regulated by submucosal glands and epithelial goblet cells. The role and especially the number of the latter are quite debatable. The present study compares the distribution and density of goblet cells in the inferior turbinates of patients with perennial allergic and nonallergic rhinitis to normal controls. The periodic acid Schiff-alcian blue whole-mount method was used to identify and count their number. Goblet cell distribution was found nonhomogeneous, and considerable variations were observed among adjacent localities of the same specimen. The mean number of goblet cells per mm2 was 6499 in normal controls (n = 12), 6818 in patients with perennial allergic rhinitis (n = 13), and 6801 in patients with perennial nonallergic rhinitis (n = 18). Statistical analysis confirmed that the density of goblet cells did not differ significantly between patients with and without allergy, as well as between each group of patients and controls. Therefore, it could be concluded that the number of goblet cells in the inferior turbinate is not influenced by the presence of perennial allergic or nonallergic rhinitis.

scholarly journals LPS Exposure in Early Life Protects Against Mucus Hypersecretion in Ovalbumin-Induced Asthma by Down-Regulation of the IL-13 and JAK-STAT6 Pathways

2018 ◽  
Vol 46 (3) ◽  
pp. 1263-1274 ◽  
Author(s):  
Fengxia Ding ◽  
Bo Liu ◽  
Wenjing Zou ◽  
Daiyin Tian ◽  
Qubei Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Periodic Acid ◽  
Mucus Secretion ◽  
Periodic Acid Schiff ◽  
Mucus Hypersecretion ◽  
Asthma Model ◽  
Pas Staining ◽  
Pre Treatment

Background/Aims: Previous studies have shown that lipopolysaccharide (LPS) exposure may have a protective effect on asthma by reducing airway hyper-responsiveness, airway inflammation and serum IgE levels. However, there are few studies investigating the effect of LPS on mucous secretion in asthma. In this study, we evaluate the relationship between LPS pre-treatment in infant mice and airway mucus hypersecretion in an OVA (ovalbumin)-induced asthma model, and further explore the mechanisms behind this effect. Methods: Mice were pre-treated with LPS by intranasal instillation (i.n.) from the 3rd day of life for 10 consecutive days before the OVA-induced asthma model was established. In order to detect mucus secretion, periodic acid-Schiff (PAS) staining was carried out, and the expression of Muc5ac was detected. The IL-13 levels in Bronchoalveolar lavage fluid (BALF) and lung tissue were also detected. In vitro, the expression of Muc5ac mRNA and protein was quantified in IL-13-stimulated 16HBE cells with or without LPS pre-treatment. In addition, proteins in the JAK2/STAT6 pathway, transcription factors (forkhead box transcription factor A2 (FOXA2), activation protein-1(AP-1), NF-κB), and the levels of reactive oxygen species (ROS) were also measured in vivo and in vitro. Results: LPS pre-treatment reduced mucus secretion, as demonstrated by decreased PAS staining and muc5ac expression. Further exploration of the underlying mechanisms of this phenomenon revealed that LPS pre-treatment decreased the production of IL-13, IL-13 induced ROS synthesis was reduced, and the JAK2/STAT6 pathway was inhibited. Decreased stat6 increased transcription factor FOXA2, and the relatively increased FOXA2 further decreased the level of Muc5ac and mucous hypersecretion in OVA-induced asthma. Conclusions: LPS pre-treatment ameliorated mucus hypersecretion in an OVA-induced asthma model by inhibition of IL-13 production and by further inhibiting the JAK2/STAT6 pathway and ROS activity, and up-regulating expression of FOXA2.

scholarly journals Comparison of asthma phenotypes in OVA-induced mice challenged via inhaled and intranasal routes

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dong Im Kim ◽  
Mi-Kyung Song ◽  
Kyuhong Lee
Keyword(s):  
Intranasal Administration ◽  
Inflammatory Responses ◽  
Periodic Acid ◽  
Mode Of Delivery ◽  
Allergen Challenge ◽  
Lavage Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Periodic Acid Schiff ◽  
Mucus Production ◽  
Pas Staining

Abstract Background The respiratory system is exposed to various allergens via inhaled and intranasal routes. Murine models of allergic lung disease have been developed to clarify the mechanisms underlying inflammatory responses and evaluate the efficacy of novel therapeutics. However, there have been no comparative studies on differences in allergic phenotypes following inhaled vs. intranasal allergen challenge. In this study, we compared the asthmatic features of mice challenged via different routes following allergen sensitization and investigated the underlying mechanisms. Methods To establish ovalbumin (OVA)-induced allergic asthma models, BALB/c mice were sensitized to 20 μg OVA with 1 mg aluminum hydroxide by the intraperitoneal route and then challenged by inhalation or intranasal administration with 5% OVA for 3 consecutive days. Cellular changes and immunoglobulin (Ig) E levels in bronchoalveolar lavage fluid (BALF) and serum, respectively, were assessed. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. Levels of T helper (Th)2 cytokines including interleukin (IL)-4, -5, and -13 in BALF and epithelial cytokines including IL-25 and -33 in BALF and lung tissues were measured by enzyme-linked immunosorbent assay and western blotting. Airway hyperresponsiveness (AHR) was evaluated by assessing airway resistance (Rrs) and elastance (E) via an invasive method. Results OVA-sensitized and challenged mice showed typical asthma features such as airway inflammation, elevated IgE level, and AHR regardless of the challenge route. However, H&E staining showed that inflammation of pulmonary vessels, alveolar ducts, and alveoli were enhanced by inhaled as compared to intranasal OVA challenge. PAS staining showed that intranasal OVA challenge induced severe mucus production accompanied by inflammation in bronchial regions. In addition, Th2 cytokine levels in BALF and AHR in lung were increased to a greater extent by inhalation than by intranasal administration of OVA. Epithelial cytokine expression, especially IL-25, was increased in the lungs of mice in the inhaled OVA challenge group. Conclusion OVA-sensitized mice exhibit different pathophysiological patterns of asthma including expression of epithelial cell-derived cytokines depending on the OVA challenge route. Thus, some heterogeneous phenotypes of human asthma can be replicated by varying the mode of delivery after OVA sensitization.

Ultrastructure of the Parotid Gland of the Nine-Banded Armadillo

1977 ◽  
Vol 35 ◽  
pp. 640-641
Author(s):  
J. R. Ruby
Keyword(s):  
Endoplasmic Reticulum ◽  
Parotid Gland ◽  
Periodic Acid ◽  
Acinar Cells ◽  
Duct System ◽  
Parotid Glands ◽  
Dasypus Novemcinctus ◽  
Anterior Portion ◽  
Periodic Acid Schiff ◽  
Thin Sections

Parotid glands were obtained from five adult (four male and one female) armadillos (Dasypus novemcinctus) which were perfusion-fixed. The glands were located in a position similar to that of most mammals. They extended interiorly to the anterior portion of the submandibular gland.In the light microscope, it was noted that the acini were relatively small and stained strongly positive with the periodic acid-Schiff (PAS) and alcian blue techniques, confirming the earlier results of Shackleford (1). Based on these qualities and other structural criteria, these cells have been classified as seromucous (2). The duct system was well developed. There were numerous intercalated ducts and intralobular striated ducts. The striated duct cells contained large amounts of PAS-positive substance.Thin sections revealed that the acinar cells were pyramidal in shape and contained a basally placed, slightly flattened nucleus (Fig. 1). The rough endoplasmic reticulum was also at the base of the cell.

Detection of Carriers in Glanzmann's Thrombasthenia

1983 ◽  
Vol 49 (03) ◽  
pp. 182-186
Author(s):  
G T E Zonneveld ◽  
E F van Leeuwen ◽  
A Sturk ◽  
J W ten Cate
Keyword(s):  
Bleeding Time ◽  
Periodic Acid ◽  
Type I ◽  
Clot Retraction ◽  
Periodic Acid Schiff ◽  
Glanzmann’S Thrombasthenia ◽  
Aggregation Response ◽  
Glanzmann's Thrombasthenia ◽  
Sds Page ◽  
Reduced State

SummaryQuantitative glycoprotein (GP) analysis of whole platelets or platelet membranes was performed by SDS-polyacrylamide gelelectrophoresis (SDS-PAGE) and periodic acid Schiff staining in the families of two unrelated Glanzmann’s thrombasthenia (GT) patients. Each family consisted of two symptom free parents, a symptom free daughter and a GT daughter. All symptom free members had a normal bleeding time, clot retraction and platelet aggregation response to adenosine 5’-diphosphate (ADP), collagen and adrenalin. Platelet Zw* antigen was normally expressed in these subjects. GT patiens, classified as a type I and II subject, showed reduced amounts of GP lib and of GP nia. Analysis of isolated membranes in the non-reduced state, however, showed that the amount of GP Ilia was also reduced in three of the four parents, whereas one parent (of the GT type I patient) and the two unaffected daughters had normal amounts of GP Ilia. Quantitative SDS-PAGE may therefore provide a method for the detection of asymptomatic carriers in GT type I and II.

Swim bladder mycosis in farmed rainbow trout Oncorhynchus mykiss caused by Phoma herbarum and experimental verification of pathogenicity

2020 ◽  
Vol 138 ◽  
pp. 237-246 ◽  
Author(s):  
J Řehulka ◽  
A Kubátová ◽  
V Hubka
Keyword(s):  
Rainbow Trout ◽  
Histopathological Examination ◽  
Periodic Acid ◽  
Bladder Wall ◽  
Swim Bladder ◽  
Cell Reactivity ◽  
Periodic Acid Schiff ◽  
Posterior Portion ◽  
Hepatic Congestion ◽  
Phoma Herbarum

In this study, spontaneous swim bladder mycosis was documented in a farmed fingerling rainbow trout from a raceway culture system. At necropsy, the gross lesions included a thickened swim bladder wall, and the posterior portion of the swim bladder was enlarged due to massive hyperplasia of muscle. A microscopic wet mount examination of the swim bladder contents revealed abundant septate hyphae, and histopathological examination showed periodic acid-Schiff-positive mycelia in the lumen and wall of the swim bladder. Histopathological examination of the thickened posterior swim bladder revealed muscle hyperplasia with expansion by inflammatory cells. The causative agent was identified as Phoma herbarum through morphological analysis and DNA sequencing. The disease was reproduced in rainbow trout fingerlings using intraperitoneal injection of a spore suspension. Necropsy in dead and moribund fish revealed extensive congestion and haemorrhages in the serosa of visceral organs and in liver and abdominal serosanguinous fluid. Histopathological examination showed severe hepatic congestion, sinusoidal dilatation, Kupffer cell reactivity, leukostasis and degenerative changes. Fungi were disseminated to the liver, pyloric caeca, kidney, spleen and heart. Although infections caused by Phoma spp. have been repeatedly reported in fish, species identification has been hampered by extensive taxonomic changes. The results of this study confirmed the pathogenicity of P. herbarum in salmonids by using a reliably identified strain during experimental fish infection and provides new knowledge regarding the course of infection.

Erdheim-Chester Disease Presenting with Histiocytic Colitis and Cytokine Storm

2017 ◽  
Vol 26 (2) ◽  
pp. 183-187
Author(s):  
George P. Christophi ◽  
Yeshika Sharma ◽  
Quader Farhan ◽  
Umang Jain ◽  
Ted Walker ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Poor Response ◽  
Rare Type ◽  
Periodic Acid Schiff ◽  
Hematopoietic Stem ◽  
Hemodynamic Compromise ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease ◽  
Segmental Colitis

Background: Non-Langerhans histiocytosis is a group of inflammatory lymphoproliferative disorders originating from non-clonal expansion of hematopoietic stem cells into cytokine-secreting dendritic cells or macrophages. Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans cell histiocytosis characterized by tissue inflammation and injury caused by macrophage infiltration and histologic findings of foamy histiocytes. Often ECD involves the skeleton, retroperitoneum and the orbits. This is the first report documenting ECD manifesting as segmental colitis and causing cytokine-release syndrome.Case presentation: A 68-year old woman presented with persistent fever without infectious etiology and hematochezia. Endoscopy showed segmental colitis and pathology revealed infiltration of large foamy histiocytes CD3-/CD20-/CD68+/CD163+/S100- consistent with ECD. The patient was empirically treated with steroids but continued to have fever and developed progressive distributive shock.Conclusion: This case report describes the differential diagnosis of infectious and immune-mediated inflammatory and rheumatologic segmental colitis. Non-Langerhans histiocytosis and ECD are rare causes of gastrointestinal inflammation. Prompt diagnosis is imperative for the appropriate treatment to prevent hemodynamic compromise due to distributive shock or gastrointestinal bleeding. Importantly, gastrointestinal ECD might exhibit poor response to steroid treatment and other potential treatments including chemotherapy, and biologic treatments targeting IL-1 and TNF-alpha signaling should be considered.Abbreviations: AFB: acid-fast bacilli; ECD: Erdheim-Chester Disease; IBD: inflammatory bowel disease; PASD: periodic acid-Schiff with diastase; TB: tuberculosis

scholarly journals Ectopic atrial arrhythmias arising from canine thoracic veins during in vivo stellate ganglia stimulation

2008 ◽  
Vol 295 (2) ◽  
pp. H691-H698 ◽  
Author(s):  
Alex Y. Tan ◽  
Shengmei Zhou ◽  
Byung Chun Jung ◽  
Masahiro Ogawa ◽  
Lan S. Chen ◽  
...  
Keyword(s):  
Pulmonary Vein ◽  
Sinus Node ◽  
Periodic Acid ◽  
Sympathetic Innervation ◽  
Sympathetic Nerves ◽  
Atrial Arrhythmias ◽  
Periodic Acid Schiff ◽  
Stellate Ganglia ◽  
Ectopic Beats

The purpose of the present study was to determine whether thoracic veins may act as ectopic pacemakers and whether nodelike cells and rich sympathetic innervation are present at the ectopic sites. We used a 1,792-electrode mapping system with 1-mm resolution to map ectopic atrial arrhythmias in eight normal dogs during in vivo right and left stellate ganglia (SG) stimulation before and after sinus node crushing. SG stimulation triggered significant elevations of transcardiac norepinephrine levels, sinus tachycardia in all dogs, and atrial tachycardia in two of eight dogs. Sinus node crushing resulted in a slow junctional rhythm (51 ± 6 beats/min). Subsequent SG stimulation induced 20 episodes of ectopic beats in seven dogs and seven episodes of pulmonary vein tachycardia in three dogs (cycle length 273 ± 35 ms, duration 16 ± 4 s). The ectopic beats arose from the pulmonary vein ( n = 11), right atrium ( n = 5), left atrium ( n = 2), and the vein of Marshall ( n = 2). There was no difference in arrhythmogenic effects of left vs. right SG stimulation (13/29 vs. 16/29 episodes, P = nonsignificant). There was a greater density of periodic acid Schiff-positive cells ( P < 0.05) and sympathetic nerves ( P < 0.05) at the ectopic sites compared with other nonectopic atrial sites. We conclude that, in the absence of a sinus node, thoracic veins may function as subsidiary pacemakers under heightened sympathetic tone, becoming the dominant sites of initiation of focal atrial arrhythmias that arise from sites with abundant sympathetic nerves and periodic acid Schiff-positive cells.

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