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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:134

Article

Reeves, Stephen R.^1,2  Kolstad, Tessa²  Lien, Tin-Yu²  Elliott, Molly^1,2  Ziegler, Steven F.³  Wight, Thomas N.³  Debley, Jason S.^1,2 

[1] Univ Washington, Seattle Childrens Hosp, Div Pulm Med, Seattle, WA 98195 USA

[2] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA

[3] Benaroya Res Inst, Seattle, WA USA

关键词: Asthma;    children;    airway remodeling;    epithelial cells;    human lung fibroblasts;    extracellular matrix;    collagen I;    collagen III;    hyaluronic acid;    fibronectin;    TGF-beta 2;   

DOI  :  10.1016/j.jaci.2014.04.007

来源: Elsevier

【 摘 要 】

Background: 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. Objectives: We sought to determine whether AECs from asthmatic children differentially regulate HLF expression of ECM constituents. Methods: 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 E-2 synthase (PGE2S) expression by AECs were assessed by using RT-PCR. TGF-beta 1 and TGF-beta 2 concentrations in media were measured by using ELISA. Results: 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-beta 2 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). Conclusions: 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.

【 授权许可】

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