Channel functions of claudins in the organization of biological systems

Meoli, Luca; Günzel, Dorothee

doi:10.1016/j.bbamem.2020.183344

Cited by 20 publications

(20 citation statements)

References 154 publications

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“…At the BCSFB, the permeability is determined by TJ, specifically the Claudin-family proteins. Claudin-1, -2, -3 are highly expressed in the CP, and have been shown to be sensitive to inflammation [ 64 – 67 ]. In our analysis, Claudin-2 was downregulated and structurally disorganized within CP epithelial cells, displaying a ruffled shape upon infection.…”

Section: Discussionmentioning

confidence: 99%

Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis

Figueiredo

Steffen

Morton

et al. 2022

J Neuroinflammation

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Background Toxoplasma gondii (T. gondii) is a highly successful parasite being able to cross all biological barriers of the body, finally reaching the central nervous system (CNS). Previous studies have highlighted the critical involvement of the blood–brain barrier (BBB) during T. gondii invasion and development of subsequent neuroinflammation. Still, the potential contribution of the choroid plexus (CP), the main structure forming the blood–cerebrospinal fluid (CSF) barrier (BCSFB) have not been addressed. Methods To investigate T. gondii invasion at the onset of neuroinflammation, the CP and brain microvessels (BMV) were isolated and analyzed for parasite burden. Additionally, immuno-stained brain sections and three-dimensional whole mount preparations were evaluated for parasite localization and morphological alterations. Activation of choroidal and brain endothelial cells were characterized by flow cytometry. To evaluate the impact of early immune responses on CP and BMV, expression levels of inflammatory mediators, tight junctions (TJ) and matrix metalloproteinases (MMPs) were quantified. Additionally, FITC-dextran was applied to determine infection-related changes in BCSFB permeability. Finally, the response of primary CP epithelial cells to T. gondii parasites was tested in vitro. Results Here we revealed that endothelial cells in the CP are initially infected by T. gondii, and become activated prior to BBB endothelial cells indicated by MHCII upregulation. Additionally, CP elicited early local immune response with upregulation of IFN-γ, TNF, IL-6, host-defence factors as well as swift expression of CXCL9 chemokine, when compared to the BMV. Consequently, we uncovered distinct TJ disturbances of claudins, associated with upregulation of MMP-8 and MMP-13 expression in infected CP in vivo, which was confirmed by in vitro infection of primary CP epithelial cells. Notably, we detected early barrier damage and functional loss by increased BCSFB permeability to FITC-dextran in vivo, which was extended over the infection course. Conclusions Altogether, our data reveal a close interaction between T. gondii infection at the CP and the impairment of the BCSFB function indicating that infection-related neuroinflammation is initiated in the CP.

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Section: Discussionmentioning

confidence: 99%

Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis

Figueiredo

Steffen

Morton

et al. 2022

J Neuroinflammation

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“…Because the experiments were carried out in symmetrical solutions with no chemical gradient present, the rise in I sc clearly reflects transcellular transport, most likely energized by the basolateral Na + /K + -ATPase. In addition, the removal of Ca 2+ is known to enhance the permeability of the paracellular pathway by the decoupling of tight junction proteins [ 47 , 48 ], which may explain part of the rise in G t .…”

Section: Discussionmentioning

confidence: 99%

The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3− by the Porcine Colon

Manneck

Manz

Braun³

et al. 2021

IJMS

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A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·l−1 cinnamaldehyde induced increases in short circuit current (ΔIsc) and conductance (ΔGt) across the colon that were higher than those across the jejunum or after 1 mmol·l−1 thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·l−1 quinidine or the bilateral replacement of 120 Na+, 120 Cl− or 25 HCO3− reduced ΔGt, while the removal of Ca2+ enhanced ΔGt with ΔIsc numerically higher. ΔIsc decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na+ or 25 HCO3−. The removal of 120 Cl− had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO3− via apical CFTR and basolateral Na+-HCO3− cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1.

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“…Claudins: Claudins appear to be central to the formation of a paracellular permeability barrier and the small ion- and small solute-selective pathways across this barrier (for reviews, see, [ 28 , 93 , 121 , 122 , 123 ]). As described above, manipulation of claudin content alters paracellular permeability to both small ions and macromolecules in predictable manners.…”

Section: What Cell Components Are Part Of the Leak Pathway?mentioning

confidence: 99%

The Epithelial Cell Leak Pathway

Monaco

Ovryn

Axis

et al. 2021

IJMS

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The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. Many aspects of the Leak Pathway, such as its molecular mechanism, its properties, and its regulation, remain controversial. In this review, we provide a historical background to the evolution of the Leak Pathway concept from the initial examinations of paracellular permeability. We then discuss current information about the properties of the Leak Pathway and present current theories for the Leak Pathway. Finally, we discuss some recent research suggesting a possible molecular basis for the Leak Pathway.

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Channel functions of claudins in the organization of biological systems

Cited by 20 publications

References 154 publications

Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis

Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis

The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3− by the Porcine Colon

The Epithelial Cell Leak Pathway

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