Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells.

08:00 EDT 14th August 2019 | BioPortfolio

Summary of "Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells."

The choroid plexus (CP), composed of capillaries surrounded by a barrier epithelium, is the main producer of cerebrospinal fluid (CSF). The CP epithelium regulates the transport of ions and water between the blood and the ventricles, contributing to CSF production and composition. Several studies suggest a connection between the cation channel Transient Receptor Potential Vanilloid-4 (TRPV4) and transepithelial ion movement. TRPV4 is a non-selective, calcium permeable cation channel present in CP epithelia reported to be activated by cytokines and inflammatory mediators. Utilizing the PCP-R (porcine choroid plexus- Riems) cell line, we investigated the effects of various cytokines and inflammatory mediators on TRPV4-mediated activity. Select pro-inflammatory cytokines (TNF-α, IL-1β, TGF-β1) had inhibitory effects on TRPV4-stimulated transepithelial ion flux and permeability changes whereas anti-inflammatory cytokines (IL-10, IL-4, IL-6) had none. Quantitative mRNA analysis showed that these cytokines had no effect on TRPV4 transcription levels. Inhibition of the transcription factor NF-κB, involved in the production and regulation of several inflammatory cytokines, inhibited TRPV4-mediated activity, suggesting a link between TRPV4 and cytokine production. Contrary to published studies, the pro-inflammatory mediator arachidonic acid (AA) had inhibitory rather than stimulatory effects on TRPV4-mediated responses. However, inhibition of AA metabolism also caused inhibitory effects on TRPV4, suggesting a complex interaction of AA and its metabolites in the regulation of TRPV4 activity. Together these data imply that TRPV4 activity is involved in the inflammatory response; it is negatively affected by pro-inflammatory mediators. Furthermore, arachidonic acid metabolites, but not arachidonic acid itself, are positive regulators of TRPV4.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Cell physiology
ISSN: 1522-1563


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Medical and Biotech [MESH] Definitions

A usually benign neoplasm that arises from the cuboidal epithelium of the choroid plexus and takes the form of an enlarged CHOROID PLEXUS, which may be associated with oversecretion of CSF. The tumor usually presents in the first decade of life with signs of increased intracranial pressure including HEADACHES; ATAXIA; DIPLOPIA; and alterations of mental status. In children it is most common in the lateral ventricles and in adults it tends to arise in the fourth ventricle. Malignant transformation to choroid plexus carcinomas may rarely occur. (Adams et al., Principles of Neurology, 6th ed, p667; DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2072)

Benign or malignant tumors which arise from the choroid plexus of the ventricles of the brain. Papillomas (see PAPILLOMA, CHOROID PLEXUS) and carcinomas are the most common histologic subtypes, and tend to seed throughout the ventricular and subarachnoid spaces. Clinical features include headaches, ataxia and alterations of consciousness, primarily resulting from associated HYDROCEPHALUS. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2072; J Neurosurg 1998 Mar;88(3):521-8)

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A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.

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