Dataset Information

Trek1 contributes to maintaining nasal epithelial barrier integrity.

ABSTRACT: Epithelial barrier integrity is critical to maintain the homeostasis in the body. The regulatory mechanism of the epithelial barrier function has not been fully understood. This study aims to elucidate the role of the TWIK-related potassium channel-1 (Trek1) in the regulation of the epithelial barrier function of the nasal mucosa. In this study, the levels of Trek1 were assessed by real time RT-PCR and Western blotting. The epithelial barrier function of the rat nasal epithelia was evaluated by the Ussing chamber system. The results showed that Trek1 was detected in the human and rat nasal epithelia, which were significantly lower in patients and rats with allergic rhinitis than that in healthy controls. Exposure to the signature T helper 2 cytokine, interleukin (IL)-4, markedly suppressed the expression of Trek1 in the nasal mucosa via up regulating the expression of the histone deacetylase (HDAC)1. The IL-4-induced rat nasal epithelial barrier dysfunction could be blocked by HDAC1 inhibitor (Trichostatin A), or sodium butyrate, or administration of Clostridium Butyricum. We conclude that Trek1 is critical to maintain the nasal epithelial barrier function.

SUBMITTER: Jiang J

PROVIDER: S-EPMC7365316 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trek1 contributes to maintaining nasal epithelial barrier integrity.

Jiang Jing J Liu Jiang-Qi JQ Li Jing J Li Meng M Chen Hong-Bin HB Yan Hao H Mo Li-Hua LH Qiu Shu-Qi SQ Liu Zhi-Gang ZG Yang Ping-Chang PC

Scientific reports 20150317

Epithelial barrier integrity is critical to maintain the homeostasis in the body. The regulatory mechanism of the epithelial barrier function has not been fully understood. This study aims to elucidate the role of the TWIK-related potassium channel-1 (Trek1) in the regulation of the epithelial barrier function of the nasal mucosa. In this study, the levels of Trek1 were assessed by real time RT-PCR and Western blotting. The epithelial barrier function of the rat nasal epithelia was evaluated by ...[more]

PMID: 25778785

Similar Datasets

Project description:BackgroundEosinophilic chronic rhinitis with nasal polyps (eos-CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type-2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type-2 inflammation. Particular matter 2.5 (PM2.5) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM2.5 on the barrier function of the eos-CRSwNP epithelium and explored the reparative function of budesonide.MethodsSamples from noninflammatory nasal mucosa and eos-CRSwNP were collected to establish an in vitro air-liquid interface cultured model. The cells were exposed to PM2.5 at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate-labeled 4-kDa dextran, quantitative real-time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme-linked immunosorbent assay or Luminex.ResultsPM2.5 increased paracellular flux and downregulated TJ protein expression (zona occuldens-1, occludin, and claudin-1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)-8, IL-10, IL-1α, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were significantly increased in the culture medium of cells exposed to PM2.5, and budesonide significantly reduced the changes in IL-8, IL-1α, and TIMP-1.ConclusionPM2.5 impaired the barrier function of eos-CRSwNP epithelial cells and increased the permeability of large molecules. PM2.5 also increased the secretion of pro-inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.

Project description:Streptococcus pneumoniae is one of the major pathogens responsible for bacterial meningitis and neurological sequelae. The present study was conducted to identify a non-hematogenous route used by S. pneumoniae to gain access to brain tissue without causing bacteremia or pneumonia, as well as bacterial and host factors involved in this process. To investigate the molecular mechanisms and dissemination pathways of pneumococcal infection in brain tissue, mice were intranasally inoculated with S. pneumoniae strain EF3030, a clinical isolate from a patient with otitis media. Pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum, with neither bacteremia nor pneumonia observed in the present model. Immunostaining imaging revealed the presence of S. pneumoniae organisms in olfactory nerve fibers. Knockout of the ply gene encoding pneumolysin (PLY) markedly compromised the ability of the bacterial organisms to disseminate into brain tissue, whereas the dissemination efficiency of the complemented strain was restored to nearly the same level as the wild type. Notably, distinct upregulation of Gli1 and Snail1, which are involved in the transcriptional repression of junctional proteins, along with downregulation of E-cadherin, was detected in nasal lavage samples from mice infected with the wild-type or complemented strain, but not in those from mice infected with the ply mutant. Taken together, the present findings indicate that PLY induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, thus allowing pneumococcal dissemination to brain tissue that occurs in a non-hematogenous manner.IMPORTANCEBacterial meningitis, considered to be caused by bacteremia, can lead to blood-brain barrier disruption and bacterial dissemination into the central nervous system. Despite the availability of intravenously administered antibiotics with cerebrospinal fluid transferability, bacterial meningitis remains associated with high rates of morbidity and mortality. Here, we utilized Streptococcus pneumoniae strain EF3030, clinically isolated from otitis media, for the construction of a murine infection model to investigate the molecular mechanisms by which nasally colonized pneumococci disseminate into brain tissue. The obtained findings indicate that pneumolysin (PLY) induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, which facilitates pneumococcal dissemination to brain tissue in a non-hematogenous manner. Our results support the existence of an alternative route by which S. pneumoniae can reach the central nervous system and indicate the need for the development of novel therapeutic strategies, which would be an important contribution to the clinical management of bacterial meningitis.

Dataset Information

Trek1 contributes to maintaining nasal epithelial barrier integrity.

Publications

Trek1 contributes to maintaining nasal epithelial barrier integrity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets