Effects of IL-13 on Mucociliary Differentiation of Pediatric Asthmatic Bronchial Epithelial Cells

Thavagnanam, Surendran; Parker, Jeremy; McBrien, M. E.; Skibiński, Grzegorz; Heaney, Liam G.; Shields, Michael

doi:10.1203/pdr.0b013e318204edb5

Cited by 34 publications

(58 citation statements)

References 32 publications

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“…The mechanisms of RSVinduced goblet cell hyperplasia/metaplasia remain to be elucidated. However, EFG-EGF receptor interactions and exogenous IL-13 were shown recently to stimulate goblet cell hyperplasia in WD-PBEC and animal models (36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Villenave

Thavagnanam

Sarlang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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170

217

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Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.

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Section: Discussionmentioning

confidence: 99%

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Villenave

Thavagnanam

Sarlang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

170

217

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“…After 14-21 days (EpiAirway) or 20-45 days (MucilAir) of culture the epithelia are fully ciliated and electrically tight (TEER≈450 Ω cm 2 ). EpiAirway cultures are available in a number of useful insert formats, and have been successfully utilized for numerous applications including airway drug delivery (Agu et al, 2006;Leonard et al, 2005Leonard et al, , 2007, airway disease modelling (Bai et al, 2015;Freishtat et al, 2011; ALI cultures have provided insights into pathogenetic mechanisms, for example the ability of Th2 cytokines, IL-4 and IL-13, to skew bronchial epithelial cell differentiation towards goblet cell hyperplasia, increased mucin gene expression and mucous hypersecretion (Kanoh et al, 2011;Thavagnanam et al, 2011;Zuyderduyn et al, 2011). Furthermore, use of ALI cultures has allowed for comparisons of barrier properties, mucus production and other responses of epithelial cells from asthmatic and healthy subjects, as well as the demonstration that tight junctions are reduced and mucus production and inflammatory cytokine induction are increased in cultures from asthmatic subjects (as observed in vivo).…”

Section: Fully Differentiated 3d Human Airway Epithelial Modelsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

122

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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“…27,28 For the apical surface view, cultured HBE cell membranes were cut from the insert using a scalpel and were fi xed in 3% formaldehyde. For the z-stack view, the cell membrane was embedded in Tissue-Tek OCT Compound (Sakura FineTechnical Co Ltd), frozen in liquid nitrogen, and stored at -80°C.…”

Section: Immunofl Uorescent Confocal Microscopy Analysismentioning

confidence: 99%

Secretory Phospholipases A 2 Are Secreted From Ciliated Cells and Increase Mucin and Eicosanoid Secretion From Goblet Cells

Tanabe

Shimokawaji

Kanoh

et al. 2015

Chest

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BACKGROUND: Secretory phospholipases A 2 (sPLA 2 ) initiate the biosynthesis of eicosanoids, are increased in the airways of people with severe asthma, and induce mucin hypersecretion. We used IL-13-transformed, highly enriched goblet cells and differentiated (ciliary cellenriched) human bronchial epithelial cell culture to evaluate the relative contribution of ciliated and goblet cells to airway sPLA 2 generation and response. We wished to determine the primary source(s) of sPLA 2 and leukotrienes in human airway epithelial cells.

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Effects of IL-13 on Mucociliary Differentiation of Pediatric Asthmatic Bronchial Epithelial Cells

Abstract: Goblet cell hyperplasia (GCH) and decreased ciliated cells are characteristic of asthma. We examined the effects of IL-13 (2 and 20 ng/mL) on in vitro mucociliary differentiation in pediatric bronchial epithelial cells (

Cited by 34 publications

References 32 publications

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Secretory Phospholipases A 2 Are Secreted From Ciliated Cells and Increase Mucin and Eicosanoid Secretion From Goblet Cells

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