Regulation of Tight Junctions in Upper Airway Epithelium

Kojima, Takashi; Go, Mitsuru; Takano, Kenichi; Kurose, Makoto; Ohkuni, Tsuyoshi; Koizumi, Jun–ichi; Kamekura, Ryuta; Ogasawara, Nagahisa; Takao, Masaki; Fuchimoto, Jun; Obata, Kazufumi; Hirakawa, Satoshi; Nomura, Kazuhiro; Keira, Takashi; Miyata, Ryou; Fujii, Nobuhiro; Tsutsumi, Hiroyuki; Himi, Tetsuo; Sawada, Norimasa

doi:10.1155/2013/947072

Cited by 128 publications

(119 citation statements)

References 86 publications

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“…Airway epithelial cells form intercellular tight junctions via multiprotein complexes. We found that Y-27632 treatment downregulated expression of four genes that are essential to forming these junctions (36). These included the occludin gene and claudin genes 1, 4, 7, and 8 ( Figure 6D, Table E5).…”

Section: Y-27632 Treatment Modulates Expression Of Genes Involved In mentioning

confidence: 88%

Airway Progenitor Clone Formation Is Enhanced by Y-27632–Dependent Changes in the Transcriptome

Reynolds

Rios²,

Wesolowska-Andersen³

et al. 2016

Am J Respir Cell Mol Biol

100

124

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The application of conditional reprogramming culture (CRC) methods to nasal airway epithelial cells would allow more widespread incorporation of primary airway epithelial culture models into complex lung disease research. In this study, we adapted the CRC method to nasal airway epithelial cells, investigated the growth advantages afforded by this technique over standard culture methods, and determined the cellular and molecular basis of CRC cell culture effects. We found that the CRC method allowed the production of 7.1 3 10 10 cells after 4 passages, approximately 379 times more cells than were generated by the standard bronchial epithelial growth media (BEGM) method. These nasal airway epithelial cells expressed normal basal cell markers and could be induced to form a mucociliary epithelium. Progenitor cell frequency was significantly higher using the CRC method in comparison to the standard culture method, and progenitor cell maintenance was dependent on addition of the Rho-kinase inhibitor Y-27632. Wholetranscriptome sequencing analysis demonstrated widespread gene expression changes in Y-27632-treated basal cells. We found that Y-27632 treatment altered expression of genes fundamental to the formation of the basal cell cytoskeleton, cell-cell junctions, and cell-extracellular matrix (ECM) interactions. Importantly, we found that Y-27632 treatment up-regulated expression of unique basal cell intermediate filament and desmosomal genes. Conversely, Y-27632 down-regulated multiple families of protease/antiprotease genes involved in ECM remodeling. We conclude that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification.

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Section: Y-27632 Treatment Modulates Expression Of Genes Involved In mentioning

confidence: 88%

Airway Progenitor Clone Formation Is Enhanced by Y-27632–Dependent Changes in the Transcriptome

Reynolds

Rios²,

Wesolowska-Andersen³

et al. 2016

Am J Respir Cell Mol Biol

100

124

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“…Besides its role as a selective and highly regulated physical barrier through the establishment of the intercellular apical junctional complexes between neighbouring airway epithelial cells (AECs) [8][9][10][11], airway epithelium also acts as a critical orchestrator of the airway immune response through the secretion of a wide repertoire of molecules, including antimicrobial peptides and proteins (eg, lysozyme, defensins, and protease inhibitors), antioxidants (eg, superoxide dismutase and glutathione), chemokines, and cytokines, in response to environmental stimuli [2,[12][13][14].…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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“…The nasal epithelium is a highly regulated, impermeable barrier formed by tight junctions (Takano et al, 2005;Holgate, 2008;Kojima et al, 2013a). Tight junctions are the most apical components of intercellular junctional complexes and they have fence and barrier functions in normal epithelial and endothelial cells (Schneeberger & Lynch, 1992;Gumbiner, 1993;Cereijido et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells

Kojima

Kondoh

Keira³

et al. 2015

Drug Delivery

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Objective: Intranasal insulin administration has therapeutic potential for Alzheimer's disease and in intranasal administration across the nasal mucosa, the paracellular pathway regulated by tight junctions is important. The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) binds the tight junction protein claudin and disrupts the tight junctional barrier without a cytotoxic effect. The C-CPE mutant called C-CPE 194 binds only to claudin-4, whereas the C-CPE 194 mutant called C-CPE m19 binds not only to claudin-4 but also to claudin-1. Methods: In the present study, to investigate the effects of C-CPE mutants on the tight junctional functions of human nasal epithelial cells (HNECs) and on the permeability of human recombinant insulin across the cells, HNECs were treated with C-CPE 194 and C-CPE m19. Results: C-CPE 194 and C-CPE m19 disrupted the barrier and fence functions without changes in expression of claudin-1, -4, -7, and occludin or cytotoxicity, whereas they transiently increased the activity of ERK1/2 phosphorylation. The disruption of the barrier function caused by C-CPE 194 and C-CPE m19 was prevented by pretreatment with the MAPKK inhibitor U0126. Furthermore, C-CPE 194 and C-CPE m19 significantly enhanced the permeability of human recombinant insulin across HNECs and the permeability was also inhibited by U0126. Conclusion: These findings suggest that C-CPE mutants 194 and m19 can regulate the permeability of insulin across HNECs via the MAPK pathway and may play a crucial role in therapy for the diseases such as Alzheimer's disease via the direct intranasal insulin administration.

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Regulation of Tight Junctions in Upper Airway Epithelium

Cited by 128 publications

References 86 publications

Airway Progenitor Clone Formation Is Enhanced by Y-27632–Dependent Changes in the Transcriptome

Airway Progenitor Clone Formation Is Enhanced by Y-27632–Dependent Changes in the Transcriptome

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells

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