Identification of histone acetylation in a murine model of allergic asthma by proteomic analysis

2020 ◽  
pp. 153537022098034
Author(s):  
Yuan Ren ◽  
Menglu Li ◽  
Shiyao Bai ◽  
Lingfei Kong ◽  
Xinming Su
Keyword(s):  
Smooth Muscle ◽  
Epithelial Cells ◽  
Smooth Muscle Cells ◽  
Histone Acetylation ◽  
Allergic Asthma ◽  
Inflammatory Cells ◽  
Muscle Cells ◽  
Airway Epithelial Cells ◽  
Whole Body ◽  
Airway Epithelial

The pathogenesis of asthma is closely related to histone acetylation modification, but the specific acetylation sites related to this process remain indistinct. Herein, our study sought to identify differentially modified acetylation sites and their expression distribution in cells involved in asthma in lung tissues. The airway hyper-responsiveness, inflammation, and remodeling were assessed by non-invasive whole-body plethysmography, ELISA, and hematoxylin-eosin staining to confirm the successful establishment of the allergic asthma model. Afterward, the differentially modified acetylation sites in asthmatic lung tissues were identified and validated by using proteomics and western blotting, respectively. The immunohistochemistry analysis was applied to reveal the distribution of identified acetylation sites in asthmatic lung tissues. A total of 15 differentially modified acetylation sites, including 13 upregulated (H3K9ac, H3K14ac, H3K18ac, H3K23ac,H3K27ac, H3K36ac, H2B1KK120ac, H2B2BK20ac, H2BK16ac, H2BK20ac, H2BK108ac, H2BK116ac, and H2BK120ac) and 2 downregulated (H2BK5ac and H2BK11ac) sites were identified and validated. Furthermore, immunohistochemical staining of lung tissues showed that nine of the identified histone acetylation sites (H2BK5, H2BK11, H3K18, H2BK116, H2BK20, H2BK120, H3K9, H3K36, and H3K27) were differentially expressed in airway epithelial cells, and the acetylation of identified H3 histones were observed in both eosinophil and perivascular inflammatory cells. Additionally, differential expression of histone acetylation sites was also observed in nucleus of airway epithelial cells, vascular smooth muscle cells, perivascular inflammatory cells, and airway smooth muscle cells. In conclusion, we identified potential acetylation sites associated with asthma pathogenesis. These findings may contribute greatly in the search for therapeutic approaches for allergic asthma.

scholarly journals Ozone modulates IL-6 secretion in human airway epithelial and smooth muscle cells

2009 ◽  
Vol 296 (4) ◽  
pp. L674-L683 ◽  
Author(s):  
Gautam Damera ◽  
Hengjiang Zhao ◽  
Miao Wang ◽  
Michael Smith ◽  
Christopher Kirby ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Airway Epithelial Cells ◽  
Ozone Exposure ◽  
Airway Epithelial ◽  
Independent Manner ◽  
Structural Cell ◽  
Human Airway ◽  
Coculture Model

Although ozone enhances leukocyte function and recruitment in airways, the direct effect of ozone in modulating structural cell-derived inflammatory mediators remains unknown. Using a coculture model comprised of differentiated human airway epithelial cells (NHBE) and smooth muscle cells (ASM), we postulate that ozone regulates IL-6 secretion in basal and cytokine-primed structural cells. Air-liquid interface (ALI) cultures of NHBE cells underwent differentiation as determined by mucin secretion, transepithelial electrical resistance (TEER), and ultrastructure parameters. Whereas TNF enhanced basal secretion of IL-6 (57 ± 3%), ozone exposure at 0.6 ppm for 6 h augmented IL-6 levels in basal (41 ± 3%) and TNF- (50 ± 5%) primed cocultures compared with that derived from NHBE or ASM monolayers alone. Levels of PGE2, 6-keto-PGF1α, PGF2α, and thromboxane B2 (TxB2) levels in basal and TNF-primed cocultures revealed that ozone selectively enhanced PGE2 production in TNF- (6 ± 3-fold) primed cocultures, with little effect ( P > 0.05) on diluent-treated cultures. In accordance with ozone-induced increases in PGE2 levels, cyclooxygenase inhibition with indomethacin partially abolished IL-6 secretion. Surprisingly, indomethacin had little effect on constitutive secretion of IL-6 in cocultures, whereas indomethacin completely restored ozone-mediated TEER reduction in TNF-primed cocultures. Collectively, our data for the first time suggest a dual role of ozone in modulating IL-6 secretion and TEER outcomes in a PGE2-dependent (in presence of TNF stimulus) and -independent manner (in absence of cytokine stimulus).

scholarly journals Heterogeneity of transcription factor expression and regulation in human airway epithelial and smooth muscle cells

2007 ◽  
Vol 293 (2) ◽  
pp. L453-L462 ◽  
Author(s):  
Alfredo Panebra ◽  
Mary Rose Schwarb ◽  
Clare B. Glinka ◽  
Stephen B. Liggett
Keyword(s):  
Smooth Muscle ◽  
Transcription Factors ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cell Type ◽  
Human Airway ◽  
Conditional Expression

Transcription factors represent a major mechanism by which cells establish basal and conditional expression of proteins, the latter potentially being adaptive or maladaptive in disease. The complement of transcription factors in two major structural cells of the lung relevant to asthma, airway epithelial and smooth muscle cells, is not known. A plate-based platform using nuclear extracts from these cells was used to assess potential expression by binding to oligonucleotide consensus sequences representing >300 transcription factors. Four conditions were studied: basal, β-agonist exposure, culture under proasthmatic conditions (IL-13, IL-4, TGF-β, and leukotriene D4), and the dual setting of β-agonist with proasthmatic culture. Airway epithelial cells expressed 70 transcription factors, whereas airway smooth muscle expressed 110. High levels of multiple transcription factors not previously recognized as being expressed in these cells were identified. Moreover, expression/ binding patterns under these conditions revealed extreme discordance in the direction and magnitude of change between the cell types. Singular (one cell type displayed regulation) and antithetic (both cell types underwent expression changes but in opposite directions) regulation dominated these patterns, with concomitant regulation in both cell types being rare (<10%). β-Agonist evoked up- and downregulation of transcription factors, which was highly influenced by the proasthmatic condition, with little overlap of factors regulated by β-agonists under both conditions. Together, these results reveal complex, cell type-dependent networks of transcription factors in human airway epithelium and smooth muscle that are dynamically regulated in unique ways by β-agonists and inflammation. These factors may represent additional components in asthma pathophysiology or potential new drug targets.

scholarly journals Human airway smooth muscle cells secrete amphiregulin via bradykinin/COX-2/PGE2, inducing COX-2, CXCL8, and VEGF expression in airway epithelial cells

2015 ◽  
Vol 309 (3) ◽  
pp. L237-L249 ◽  
Author(s):  
Karl Deacon ◽  
Alan J. Knox
Keyword(s):  
Smooth Muscle ◽  
Epithelial Cells ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Airway Epithelial Cells ◽  
Airway Smooth Muscle Cells ◽  
Airway Epithelial ◽  
Human Airway Smooth Muscle ◽  
Cox 2 ◽  
Stimulation Of

Human airway smooth muscle cells (HASMC) contribute to asthma pathophysiology through an increased smooth muscle mass and elevated cytokine/chemokine output. Little is known about how HASMC and the airway epithelium interact to regulate chronic airway inflammation and remodeling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and proinflammatory roles and increased expression in the lungs of asthma patients. Here we show that bradykinin (BK) stimulation of HASMC increases amphiregulin secretion in a mechanism dependent on BK-induced COX-2 expression, increased PGE2 output, and the stimulation of HASMC EP2 and EP4 receptors. Conditioned medium from BK treated HASMC induced CXCL8, VEGF, and COX-2 mRNA and protein accumulation in airway epithelial cells, which were blocked by anti-amphiregulin antibodies and amphiregulin siRNA, suggesting a paracrine effect of HASMC-derived amphiregulin on airway epithelial cells. Consistent with this, recombinant amphiregulin induced CXCL8, VEGF, and COX-2 in airway epithelial cells. Finally, we found that conditioned media from amphiregulin-stimulated airway epithelial cells induced amphiregulin expression in HASMC and that this was dependent on airway epithelial cell COX-2 activity. Our study provides evidence of a dynamic axis of interaction between HASMC and epithelial cells that amplifies CXCL8, VEGF, COX-2, and amphiregulin production.

scholarly journals Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1485
Author(s):  
Adrian Sowka ◽  
Pawel Dobrzyn
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Vascular Wall ◽  
Whole Body ◽  
Perivascular Adipose Tissue

Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin’s structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.

scholarly journals Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma

2017 ◽  
Vol 199 (1) ◽  
pp. 48-61 ◽  
Author(s):  
Carina Klaßen ◽  
Anna Karabinskaya ◽  
Lien Dejager ◽  
Sabine Vettorazzi ◽  
Justine Van Moorleghem ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Allergic Asthma ◽  
Airway Epithelial Cells ◽  
Airway Epithelial
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