IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct Roles in Epithelial Cell Mucin Production

Zhen, Guohua; Park, Sung Woo; Nguyenvu, Louis T.; Rodriguez, Madeleine W.; Barbeau, Rebecca; Paquet, Agnès; Erle, David J.

doi:10.1165/rcmb.2006-0180oc

Cited by 231 publications

(224 citation statements)

References 38 publications

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“…IL‐13 induces SPDEF and CLCA1 expression, both essential genes involved in the development of IL‐13‐induced MUC5AC expression (Zhen et al. 2007; Yu et al. 2010; Alevy et al.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

et al. 2017

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Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN,CLCA1, and SERPINB2. This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2‐high and Th2‐low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL‐13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin‐related genes MUC5AC and SPDEF in air–liquid interface differentiated human bronchial (ALI‐PBEC) and tracheal epithelial cells (ALI‐PTEC). Cultures were exposed to IL‐13 for 14 days followed by 5 days of IL‐13 with CS exposure. Alternatively, cultures were exposed once daily to CS for 14 days, followed by 5 days CS with IL‐13. POSTN,SERPINB2, and CLCA1 expression were measured 24 h after the last exposure to CS and IL‐13. In both models POSTN,SERPINB2, and CLCA1 expression were increased by IL‐13. CS markedly affected the IL‐13‐induced Th2 gene signature as indicated by a reduced POSTN,CLCA1, and MUC5AC expression in both models. In contrast, IL‐13‐induced SERPINB2 expression remained unaffected by CS, whereas SPDEF expression was additively increased. Importantly, cessation of CS exposure failed to restore IL‐13‐induced POSTN and CLCA1 expression. We show for the first time that CS differentially affects the IL‐13‐induced gene signature for Th2‐high asthma. These findings provide novel insights into the interaction between Th2 inflammation and cigarette smoke that is important for asthma pathogenesis and biomarker‐guided therapy in asthma.

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“…IL‐13 induces SPDEF and CLCA1 expression, both essential genes involved in the development of IL‐13‐induced MUC5AC expression (Zhen et al. 2007; Yu et al. 2010; Alevy et al.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

et al. 2017

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“…The differences in DUOX1/2 promoter regions are consistent with the highly variable transcriptional regulation of airway epithelial DUOX1 and DUOX2 in response to pro-inflammatory cytokines or to bacterial or viral stimuli (36,83,96). For example, DUOX1 mRNA expression in primary airway epithelial cultures is induced 3-5 fold by the Th2 cytokines interleukin (IL)-4 and IL-13 (83), which induce ciliatedto-mucus cell transdifferentiation and mucus hyperplasia during allergic airway inflammation (97,98). DUOX1 expression is also dramatically enhanced after hormonal differentiation of fetal lung epithelial cells to alveolar type II cells (90).…”

Section: Nadph Oxidases Within the Airway Epithelium: Duox1 And Duox2mentioning

confidence: 99%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

187

192

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The deliberate production of reactive oxygen species (ROS) by phagocyte NADPH oxidase is widely appreciated as a critical component of antimicrobial host defense. Recently, additional homologs of NADPH oxidase (NOX) have been discovered throughout the animal and plant kingdoms, which appear to possess diverse functions in addition to host defense, including cell proliferation, differentiation, and regulation of gene expression. Several of these NOX homologs are also expressed within the respiratory tract, where they participate in innate host defense as well as in epithelial and inflammatory cell signaling and gene expression, and fibroblast and smooth muscle cell proliferation, in response to bacterial or viral infection and environmental stress. Inappropriate expression or activation of NOX/DUOX during various lung pathologies suggests their specific involvement in respiratory disease. This review summarizes the current state of knowledge regarding the general functional properties of mammalian NOX enzymes, and their specific importance in respiratory tract physiology and pathology.

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“…RNA isolation and RT-PCR were performed as previously described (20). Real-time PCR was performed using the SYBR green method, as described (65). Primer sequences are available in supplemental data (Supplemental Table 4).…”

Section: Figurementioning

confidence: 99%

Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients

Araya¹,

Cambier²,

Markovics³

et al. 2007

J. Clin. Invest.

Self Cite

231

228

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Squamous metaplasia (SM) is common in smokers and is associated with airway obstruction in chronic obstructive pulmonary disease (COPD). A major mechanism of airway obstruction in COPD is thickening of the small airway walls. We asked whether SM actively contributes to airway wall thickening through alteration of epithelial-mesenchymal interactions in COPD. Using immunohistochemical staining, airway morphometry, and fibroblast culture of lung samples from COPD patients; genome-wide analysis of an in vitro model of SM; and in vitro modeling of human airway epithelial-mesenchymal interactions, we provide evidence that SM, through the increased secretion of IL-1β, induces a fibrotic response in adjacent airway fibroblasts. We identify a pivotal role for integrin-mediated TGF-β activation in amplifying SM and driving IL-1β-dependent profibrotic mesenchymal responses. Finally, we show that SM correlates with increased severity of COPD and that fibroblast expression of the integrin α v β 8 , which is the major mediator of airway fibroblast TGF-β activation, correlated with disease severity and small airway wall thickening in COPD. Our findings have identified TGF-β as a potential therapeutic target for COPD.

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IL-13 and Epidermal Growth Factor Receptor Have Critical but Distinct Roles in Epithelial Cell Mucin Production

Cited by 231 publications

References 38 publications

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients

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