Airway Fibroblast Secretory Products Enhance Cell Migration

2021 ◽  
Vol 18 ◽  
Author(s):  
Nundisa Jaulin ◽  
Ruszymah Hj Idrus ◽  
Aminuddin Saim ◽  
Wan Izlina Wan-Ibrahim ◽  
Puteri Shafinaz Abdul-Rahman ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Conditioned Medium ◽  
Airway Epithelium ◽  
Basal Medium ◽  
Airway Epithelial Cells ◽  
Secreted Proteins ◽  
Secretory Proteins ◽  
Airway Epithelial ◽  
Serum Free

Background: The nasal fibroblast secretome, which includes various cytokines, chemokines, and growth factors, promotes cell migration. Currently, the proteomics of airway fibroblast (AF) conditioned medium (AFCM) are being actively studied. Objective: This study was aimed at profiling and identifying the AF secreted proteins that can enhance wound healing of the airway epithelium and predict the potential pathway involved. Methods: Airway epithelial cells (AECs) and AFs were isolated from redundant human nasal turbinate and cultured. AFCM was collected by culturing the AFs either with serum-free airway epithelium basal medium (AECM) or with serum-free F12:DMEM (FDCM). For evaluating cell migration, the AECs were supplemented with airway epithelium medium and defined keratinocyte medium (1:1; AEDK; control), or with AEDK supplemented with 20% AECM or 20% FDCM. The mass spectrometry sample was prepared by protein precipitation, followed by gel electrophoresis and in-gel digestion. Results : AECM promoted better cell migration compared to the FDCM and the control medium. Bioinformatics analysis identified a total of 121, and 92 proteins from AECM and FDCM, respectively: 109 and 82 were identified as secreted proteins, respectively. STRING® analysis predicted that 23 proteins from the AECM and 16 proteins from the FDCM are involved in wound healing. Conclusion: Conditioned medium promotes wound healing by enhancing cell migration, and we successfully identified various secretory proteins in a conditioned medium that play important roles in wound healing.

Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure

2005 ◽  
Vol 289 (5) ◽  
pp. L842-L848 ◽  
Author(s):  
Renat Shaykhiev ◽  
Christoph Beißwenger ◽  
Kerstin Kändler ◽  
Judith Senske ◽  
Annette Püchner ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Epithelial Cells ◽  
Cell Line ◽  
Airway Epithelium ◽  
Wound Closure ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
And Migration ◽  
Proliferation And Migration

Antimicrobial peptides are endogenous antibiotics that directly inactivate microorganisms and in addition have a variety of receptor-mediated functions. LL-37/hCAP-18 is the only cathelicidin found in humans and is involved in angiogenesis and regulation of the innate immune system. The aim of the present study was to characterize the role of the peptide LL-37 in the regulation of wound closure of the airway epithelium in the cell line NCI-H292 and primary airway epithelial cells. LL-37 stimulated healing of mechanically induced wounds in monolayers of the cell line and in differentiated primary airway epithelium. This effect was detectable at concentrations of 5 μg/ml in NCI-H292 and 1 μg/ml in primary cells. The effect of LL-37 on wound healing was dependent on the presence of serum. LL-37 induced cell proliferation and migration of NCI-H292 cells. Inhibitor studies in the wound closure and proliferation assays indicated that the effects caused by LL-37 are mediated through epidermal growth factor receptor, a G protein-coupled receptor, and MAP/extracellular regulated kinase. In conclusion, LL-37 induces wound healing, proliferation, and migration of airway epithelial cells. The peptide is likely involved in the regulation of tissue homeostasis in the airways.

scholarly journals Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ian T. Stancil ◽  
Jacob E. Michalski ◽  
Duncan Davis-Hall ◽  
Hong Wei Chu ◽  
Jin-Ah Park ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Airway Epithelium ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Chronic Lung Diseases ◽  
Distal Airway ◽  
Signaling Axis

AbstractThe airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.

scholarly journals Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nadzeya Marozkina ◽  
Laura Smith ◽  
Yi Zhao ◽  
Joe Zein ◽  
James F. Chmiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Nitrogen Oxides ◽  
Airway Epithelium ◽  
Airflow Obstruction ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Human Airway Epithelial Cells

AbstractEndothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.

scholarly journals The innate immune function of airway epithelial cells in inflammatory lung disease

2015 ◽  
Vol 45 (4) ◽  
pp. 1150-1162 ◽  
Author(s):  
Pieter S. Hiemstra ◽  
Paul B. McCray ◽  
Robert Bals
Keyword(s):  
Immune Responses ◽  
Airway Epithelium ◽  
Cell Function ◽  
Developmental Regulation ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Tissue Remodelling ◽  
Wide Range ◽  
Differentiation Pathways

The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed.

The wound healing capacity of undifferentiated and differentiated airway epithelial cells in vitro

2018 ◽  
Vol 112 ◽  
pp. 163-168 ◽  
Author(s):  
Cynthia M. Schwartz ◽  
Braedyn A. Dorn ◽  
Selam Habtemariam ◽  
Cynthia L. Hill ◽  
Tendy Chiang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

Transgenic overexpression of β2-adrenergic receptors in airway epithelial cells decreases bronchoconstriction

2000 ◽  
Vol 279 (2) ◽  
pp. L379-L389 ◽  
Author(s):  
Dennis W. McGraw ◽  
Susan L. Forbes ◽  
Judith C. W. Mak ◽  
David P. Witte ◽  
Patricia E. Carrigan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Adrenergic Receptors ◽  
Airway Epithelial Cells ◽  
Airway Responsiveness ◽  
Ozone Exposure ◽  
Clara Cell ◽  
Whole Body ◽  
Airway Epithelial

Airway epithelial cells express β2-adrenergic receptors (β2-ARs), but their role in regulating airway responsiveness is unclear. With the Clara cell secretory protein (CCSP) promoter, we targeted expression of β2-ARs to airway epithelium of transgenic (CCSP-β2-AR) mice, thereby mimicking agonist activation of receptors only in these cells. In situ hybridization confirmed that transgene expression was confined to airway epithelium, and autoradiography showed that β2-AR density in CCSP-β2-AR mice was approximately twofold that of nontransgenic (NTG) mice. Airway responsiveness measured by whole body plethysmography showed that the methacholine dose required to increase enhanced pause to 200% of baseline (ED200) was greater for CCSP-β2-AR than for NTG mice (345 ± 34 vs. 157 ± 14 mg/ml; P < 0.01). CCSP-β2-AR mice were also less responsive to ozone (0.75 ppm for 4 h) because enhanced pause in NTG mice acutely increased to 77% over baseline ( P < 0.05) but remained unchanged in the CCSP-β2-AR mice. Although both groups were hyperreactive to methacholine 6 h after ozone exposure, the ED200for ozone-exposed CCSP-β2-AR mice was equivalent to that for unexposed NTG mice. These findings show that epithelial cell β2-ARs regulate airway responsiveness in vivo and that the bronchodilating effect of β-agonists results from activation of receptors on both epithelial and smooth muscle cells.

scholarly journals Tissue Factor Facilitates Wound Healing in Human Airway Epithelial Cells

CHEST Journal ◽  
2019 ◽  
Vol 155 (3) ◽  
pp. 534-539 ◽  
Author(s):  
Michael D. Davis ◽  
Isao Suzaki ◽  
Shuichi Kawano ◽  
Kosaku Komiya ◽  
Qing Cai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Tissue Factor ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

scholarly journals EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production

2014 ◽  
Vol 307 (2) ◽  
pp. L186-L196 ◽  
Author(s):  
April Kalinowski ◽  
Iris Ueki ◽  
Gundula Min-Oo ◽  
Eric Ballon-Landa ◽  
David Knoff ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Infection ◽  
Airway Epithelium ◽  
Respiratory Virus ◽  
Respiratory Viruses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Egfr Signaling ◽  
Respiratory Viral Infection ◽  
Egfr Activation

Airway epithelial cells are the primary cell type involved in respiratory viral infection. Upon infection, airway epithelium plays a critical role in host defense against viral infection by contributing to innate and adaptive immune responses. Influenza A virus, rhinovirus, and respiratory syncytial virus (RSV) represent a broad range of human viral pathogens that cause viral pneumonia and induce exacerbations of asthma and chronic obstructive pulmonary disease. These respiratory viruses induce airway epithelial production of IL-8, which involves epidermal growth factor receptor (EGFR) activation. EGFR activation involves an integrated signaling pathway that includes NADPH oxidase activation of metalloproteinase, and EGFR proligand release that activates EGFR. Because respiratory viruses have been shown to activate EGFR via this signaling pathway in airway epithelium, we investigated the effect of virus-induced EGFR activation on airway epithelial antiviral responses. CXCL10, a chemokine produced by airway epithelial cells in response to respiratory viral infection, contributes to the recruitment of lymphocytes to target and kill virus-infected cells. While respiratory viruses activate EGFR, the interaction between CXCL10 and EGFR signaling pathways is unclear, and the potential for EGFR signaling to suppress CXCL10 has not been explored. Here, we report that respiratory virus-induced EGFR activation suppresses CXCL10 production. We found that influenza virus-, rhinovirus-, and RSV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1-dependent CXCL10 production. In addition, inhibition of EGFR during viral infection augmented IRF1 and CXCL10. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies.

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