Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

Große-Onnebrink, Joerg; Werner, Claudius; Loges, Niki T.; Hörmann, K.; Blum, Andreas; Schmidt, René; Olbrich, Heike; Omran, Heymut

doi:10.1038/pr.2016.8

Cited by 21 publications

(19 citation statements)

References 43 publications

(41 reference statements)

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“…In agreement with previous studies on mammalian cells, treatment with cAMP, IL-5, IFN-γ and Prostaglandin-E2 induced enhancement in CBF of Xenopus cilia, unlike Sildenafil which did not significantly change CBF (Figure 5b). In agreement with studies in mammalian cells, Prostaglandin-E2 induces ~10% increase in CBF (Bonin et al, 1992) while IL-5 results in ~20% (Grosse-Onnebrink et al, 2016). Using our assay, we observed ~15% and 20% increase in mixing efficiency, respectively.…”

Section: The Xenopus Flow Assay Can Directly Assess the Effects Of Cb...supporting

confidence: 90%

Development of aXenopus-based assay for high-throughput evaluation of mucociliary flow

Antoniades

Koulle

Chatzifrangkeskou

et al. 2022

Preprint

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Motile cilia are organelles lining the surfaces of major organs of the human body and generate directional fluid flow. Ciliary dysfunction has been linked to an emerging class of multisystem disorders, collectively known as motile ciliopathies. Drug screening for ciliopathies is challenging due to the unavailability of high-throughput assays that can evaluate ciliary flow generation. Here, we describe the development of a unique assay that enables the direct and rapid evaluation of mucociliary flow, which simultaneously facilitates high-throughput screening of potential therapeutic agents for motile ciliopathies. The assay relies on the ability of Xenopus tadpoles to promote mixing of a two-phase differential density aqueous mixture, through the robust flow generated by the mucociliary epithelium on their epidermis. We show that the rate of phase mixing is proportional to the rate of cilia-driven flow, therefore it directly represents the effectiveness of flow generation. We also demonstrate that the assay can detect changes in ciliary flow elicited by defects in cilia, CBF modulation and rotational polarity, providing an ideal assay for the identification of CBF-modulating compounds, as potential drugs for motile ciliopathies. Importantly we use the assay to show that CBF modulating drugs can improve flow generation and could thus be used as a potential therapeutic approach in PCD patients. The assay we have developed thus represents a powerful new tool for research, as well as drug development.

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Section: The Xenopus Flow Assay Can Directly Assess the Effects Of Cb...supporting

confidence: 90%

Development of aXenopus-based assay for high-throughput evaluation of mucociliary flow

Antoniades

Koulle

Chatzifrangkeskou

et al. 2022

Preprint

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“…A number of GO terms were associated with the functions of cilia – “regulation of cilium beat frequency”, “regulation of cilium movement”, and “ciliary basal body docking”. Probably the frequency of beating of the cilia has an adaptive value in the cold, because some authors connected the beating of cilia with respiratory function [ 71 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

2017

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BackgroundMany mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals.ResultsAfter a search for publications containing keywords: “whole genome”, “transcriptome or exome sequencing data”, and “genome-wide genotyping array data” authors looked for information related to genetic signatures ascribable to positive selection in Arctic or Antarctic mammalian species. Publications related to Human, Arctic fox, Yakut horse, Mammoth, Polar bear, and Minke whale were chosen. The compendium of genes that potentially underwent positive selection in >1 of these six species consisted of 416 genes. Twelve of them showed traces of positive selection in three species. Gene ontology term enrichment analysis of 416 genes from the compendium has revealed 13 terms relevant to the scope of this study. We found that enriched terms were relevant to three major groups: terms associated with collagen proteins and the extracellular matrix; terms associated with the anatomy and physiology of cilium; terms associated with docking. We further revealed that genes from compendium were over-represented in the lists of genes expressed in the lung and liver.ConclusionsA compendium combining mammalian genes involved in adaptation to cold environment was designed, based on the intersection of positively selected genes from six Arctic and Antarctic species. The compendium contained 416 genes that have been positively selected in at least two species. However, we did not reveal any positively selected genes that would be related to cold adaptation in all species from our list. But, our work points to several strong candidate genes involved in mechanisms and biochemical pathways related to cold adaptation response in different species.Electronic supplementary materialThe online version of this article (10.1186/s12863-017-0580-9) contains supplementary material, which is available to authorized users.

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“…Secondary, acquired nongenetic defects affecting ciliary function can also be caused by factors such as cigarette smoke exposure and inflammation during asthma and chronic obstructive pulmonary disease (COPD), with studies showing that affected individuals are at higher risk of lung infections ( 17 , 61 , 183 , 209 ). Multiple ciliary defects have been reported in the asthmatic airways, ranging from decreased motility, disorientation in beat direction, and ultrastructural damage ( 136 , 137 , 185 ).…”

Section: Consequences Of Ciliary Dysfunctionmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

117

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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens including viruses, bacteria and fungi have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections is still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immuno-regulatory roles during infection will also be discussed.

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Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

Cited by 21 publications

References 43 publications

Development of aXenopus-based assay for high-throughput evaluation of mucociliary flow

Development of aXenopus-based assay for high-throughput evaluation of mucociliary flow

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

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