Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in Asthma

Lee, Pureun Haneul; Kim, Byeong Gon; Lee, Sun Hye; Lee, June Hyuck; Park, Sung Woo; Kim, Dojin; Park, Choon-Sik; Leikauf, George D.

doi:10.4168/aair.2018.10.1.25

Cited by 18 publications

(22 citation statements)

References 28 publications

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“…IFNinduced CH25H shows antiviral activities and can positively and negatively regulate the inflammatory responses of mammals (78). Mammalian TNFRSF11B (alias Osteoprotegerin), ZNRF1 and CLDN4 regulate LPS-induced cytokine and/or inflammatory responses (79)(80)(81). GVINP1 is an IFN-induced GTPase, regulating oxidative and inflammasome-related antimicrobial activities of cells in mammals (82).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of the Adaptive and Innate Immune Responses of Atlantic Salmon to Renibacterium salmoninarum Infection

et al. 2020

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Bacterial Kidney Disease (BKD), which is caused by a Gram-positive, intracellular bacterial pathogen (Renibacterium salmoninarum), affects salmonids including Atlantic salmon (Salmo salar). However, the transcriptome response of Atlantic salmon to BKD remained unknown before the current study. We used a 44K salmonid microarray platform to characterise the global gene expression response of Atlantic salmon to BKD. Fish (∼54 g) were injected with a dose of R. salmoninarum (H-2 strain, 2 × 10 8 CFU per fish) or sterile medium (control), and then head kidney samples were collected at 13 days post-infection/injection (dpi). Firstly, infection levels of individuals were determined through quantifying the R. salmoninarum level by RNA-based TaqMan qPCR assays. Thereafter, based on the qPCR results for infection level, fish (n = 5) that showed no (control), higher (H-BKD), or lower (L-BKD) infection level at 13 dpi were subjected to microarray analyses. We identified 6,766 and 7,729 differentially expressed probes in the H-BKD and L-BKD groups, respectively. There were 357 probes responsive to the infection level (H-BKD vs. L-BKD). Several adaptive and innate immune processes were dysregulated in R. salmoninarum-infected Atlantic salmon. Adaptive immune pathways associated with lymphocyte differentiation and activation (e.g., lymphocyte chemotaxis, T-cell activation, and immunoglobulin secretion), as well as antigen-presenting cell functions, were shown to be differentially regulated in response to BKD. The infection level-responsive transcripts were related to several mechanisms such as the JAK-STAT signalling pathway, B-cell differentiation and interleukin-1 responses. Sixty-five microarray-identified transcripts were subjected to qPCR validation, and they showed the same fold-change direction as microarray results. The qPCRvalidated transcripts studied herein play putative roles in various immune processes including pathogen recognition (e.g., tlr5), antibacterial activity (e.g., hamp and camp), regulation of immune responses (e.g., tnfrsf11b and socs1), T-/B-cell differentiation (e.g., ccl4, irf1 and ccr5), T-cell functions (e.g., rnf144a, il13ra1b and tnfrsf6b), and Eslamloo et al. Atlantic Salmon Response to BKD antigen-presenting cell functions (e.g., fcgr1). The present study revealed diverse immune mechanisms dysregulated by R. salmoninarum in Atlantic salmon, and enhanced the current understanding of Atlantic salmon response to BKD. The identified biomarker genes can be used for future studies on improving the resistance of Atlantic salmon to BKD.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of the Adaptive and Innate Immune Responses of Atlantic Salmon to Renibacterium salmoninarum Infection

et al. 2020

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“…The ECM is a non-cellular component in all tissues and organs and adherens junctions between cells, and are essential for the maintenance of the structural and functional integrity of organs ( 49 ). Disruption of ECM and adherens junctions may contribute to the destruction of the epithelial barrier and favor the interaction of leukocytes with endothelial cells, promoting the development of inflammation-associated diseases ( 50 ), including AIED. Cai et al ( 51 ) previously reported that the expression of ECM gene Itga5 in the basal sections of the sensory epithelium in the cochlea was positively correlated with greater hearing loss as a result to exposure to an intense noise for 2 h. Endogenous overexpression of another ECM gene, SPP1, induces Ccl5 and matrix metalloproteinase-2 activation that contributes to proinflammatory events ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Screening of genes associated with inﬂammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases

Zhang

Wang

2018

Exp Ther Med

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The current study analyzed gene expression profiles of the endolymphatic sac (ES) in rats and identified expressed genes, present in the human and rat ES, to reveal key hubs for inflammatory responses. Microarray data (accession no. E-MEXP-3022) were obtained from the European Bioinformatics Institute database, including three biological replicates of ES plus dura tissues and three replicates of pure dura tissues form rats. Differentially expressed genes (DEGs) were screened using the Linear Model for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins database followed by a module analysis via Clustering with Overlapping Neighborhood Expansion. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tool. A total of 612 DEGs were identified, including 396 upregulated and 216 downregulated genes. Gene ontology term enrichment analysis indicated DEGs were associated with cell adhesion, including α5-integrin (Itga1) and secreted phosphoprotein 1 (Spp1); T cell co-stimulation, including C-C chemokine ligand (Ccl)21 and Ccl19; and the toll-like receptor signaling pathway, including toll-like receptor (Tlr)2, Tlr7 and Tlr8. These conclusions were supported by Kyoto Encyclopedia of Genes and Genomes pathway analyses revealing extracellular matrix-receptor interaction, including Itga1 and Spp1; leukocyte transendothelial migration, includingclaudin-4 (Cldn4); and malaria, including Tlr2. The hub roles of Itga1, Cd24 and Spp1 were revealed by calculating three topological properties of the PPI network. Ccl21, Ccl19 and Cldn4 were demonstrated to be crucial following significant module analysis according to the corresponding threshold, which revealed they were enriched in inflammation pathways. Tlr7, Tlr2, granzyme m and Tlr8 were common genes associated with inflammatory responses in rat and human ES. In conclusion, abnormal expression of the aforementioned inflammation-associated genes may be associated with the development of autoimmune inner ear diseases.

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“…Among the candidate biomarkers mentioned above there are various sampling compartments that may be used in future clinical applications. Reduced ezrin expression is detected in both EBC and serum of asthma patients [70,72] and elevated levels of claudin 4 [105] and YKL40 are detected in asthmatic blood [77][78][79]. Epithelial brushings from patients with asthma have significantly lower claudin18 levels than healthy controls [106].…”

Section: Tissue Compartments For Biomarker Assessmentmentioning

confidence: 99%

Airway epithelial cell damage in asthma: mechanisms and biomarkers

Yang

Jia

et al. 2020

Preprint

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Bronchial asthma is a heterogeneous disease with complex pathological mechanisms representing different phenotypes, including severe asthma. The airway epithelium is a major site of complex pathological changes in severe asthma due, in part, to activation of inflammatory and immune mechanisms in response to noxious agents. Current imaging procedures are unable to accurately measure epithelial and airway remodeling. Damage of airway epithelial cells occurs is linked to specific phenotypes and endotypes which provides an opportunity for the identification of biomarkers reflecting epithelial, and airway, remodeling. Identification of patients with more severe epithelial disruption using biomarkers may also provide personalized therapeutic opportunities and/or markers of successful therapeutic intervention. Here, we review the evidence for ongoing epithelial cell dysregulation in the pathogenesis of asthma, the sentinel role of the airway epithelium and how understanding these molecular mechanisms provides the basis for the identification of candidate biomarkers for asthma prediction, prevention, diagnosis, treatment and monitoring.

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Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in Asthma

Cited by 18 publications

References 28 publications

Transcriptomic Profiling of the Adaptive and Innate Immune Responses of Atlantic Salmon to Renibacterium salmoninarum Infection

Transcriptomic Profiling of the Adaptive and Innate Immune Responses of Atlantic Salmon to Renibacterium salmoninarum Infection

Screening of genes associated with inﬂammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases

Airway epithelial cell damage in asthma: mechanisms and biomarkers

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