Asthmatic airway epithelial cells differentially regulate fibroblast expression of extracellular matrix components

• Published in: Journal of allergy and clinical immunology Vol. 134; no. 3; pp. 663 - 670.e1
• Main Authors: Reeves, Stephen R., Kolstad, Tessa, Lien, Tin-Yu, Elliott, Molly, Ziegler, Steven F., Wight, Thomas N., Debley, Jason S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2014; Elsevier; Elsevier Limited
• Subjects: Adolescent; Age; airway remodeling; Airway Remodeling - physiology; Allergies; Allergy and Immunology; Asthma; Biological and medical sciences; Cell Communication; Cells, Cultured; Child; children; Chronic obstructive pulmonary disease, asthma; Coculture Techniques; Collagen; collagen I; collagen III; Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type III - genetics; Collagen Type III - metabolism; epithelial cells; Extracellular matrix; Extracellular Matrix - metabolism; Family medical history; Female; Fibroblasts - pathology; Fibroblasts - physiology; fibronectin; Fibronectins - genetics; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Health care; human lung fibroblasts; Humans; Hyaluronan Synthases; hyaluronic acid; Immunopathology; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - metabolism; Lung - pathology; Male; Medical sciences; Mortality; Nitric oxide; Pathogenesis; Pneumology; Prostaglandin-E Synthases; Respiratory Mucosa - physiology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; School attendance; Smooth muscle; Studies; TGF-β2; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta2 - metabolism; Feno; HLF; IHC; PGE2S; PTGS2; hyaluronic acid; children; AEC; human lung fibroblasts; PGE2; collagen III; airway remodeling; epithelial cells; FGM; ECM; Asthma; COL1A1; COL3A1; FVC; fibronectin; collagen I; HA; TGF-β2; HAS; extracellular matrix; ALI; Immunohistochemistry; Forced vital capacity; Fraction of exhaled nitric oxide; PGE 2; Hyaluronan synthase; Hyaluronan; F eno; Human lung fibroblast; Airway epithelial cells; Air-liquid interface; Prostaglandin E 2 synthase; Prostaglandin-endoperoxide synthase 2; Fibroblast growth media; Prostaglandin E 2; Lung; Collagen type III; Remodeling; Respiratory system; Fibronectin; Respiratory tract; Regulation(control); Immunology; Collagen type I; Bronchus disease; Extracellular matrix; Obstructive pulmonary disease; Child; Human; Lung disease; Immunopathology; Respiratory disease; Transforming growth factor β2; Glycosaminoglycan; Epithelial cell; Hyaluronic acid; Fibroblast
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2014.04.007

Airway remodeling might explain lung function decline among asthmatic children. Extracellular matrix (ECM) deposition by human lung fibroblasts (HLFs) is implicated in airway remodeling. Airway epithelial cell (AEC) signaling might regulate HLF ECM expression. We sought to determine whether AECs from asthmatic children differentially regulate HLF expression of ECM constituents. Primary AECs were obtained from well-characterized atopic asthmatic (n = 10) and healthy (n = 10) children intubated during anesthesia for an elective surgical procedure. AECs were differentiated at an air-liquid interface for 3 weeks and then cocultured with HLFs from a healthy child for 96 hours. Collagen I (COL1A1), collagen III (COL3A1), hyaluronan synthase (HAS) 2, and fibronectin expression by HLFs and prostaglandin E2 synthase (PGE2S) expression by AECs were assessed by using RT-PCR. TGF-β1 and TGF-β2 concentrations in media were measured by using ELISA. COL1A1 and COL3A1 expression by HLFs cocultured with AECs from asthmatic patients was greater than that by HLFs cocultured with AECs from healthy subjects (2.2-fold, P < .02; 10.8-fold, P < .02). HAS2 expression by HLFs cocultured with AECs from asthmatic patients was 2.5-fold higher than that by HLFs cocultured with AECs from healthy subjects (P < .002). Fibronectin expression by HLFs cocultured with AECs from asthmatic patients was significantly greater than that by HLFs alone. TGF-β2 activity was increased in cocultures of HLFs with AECs from asthmatic patients (P < .05), whereas PGES2 was downregulated in AEC-HLF cocultures (2.2-fold, P < .006). HLFs cocultured with AECs from asthmatic patients showed differential expression of the ECM constituents COL1A1 and COL3A1 and HAS2 compared with HLFs cocultured with AECs from healthy subjects. These findings support a role for altered ECM production in asthmatic airway remodeling, possibly regulated by unbalanced AEC signaling.