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dc.contributor.authorBalinas, C
dc.contributor.authorCabanas, H
dc.contributor.authorStaines, D
dc.contributor.authorMarshall-Gradisnik, S
dc.date.accessioned2020-01-13T05:04:11Z
dc.date.available2020-01-13T05:04:11Z
dc.date.issued2019
dc.identifier.issn1479-5876
dc.identifier.doi10.1186/s12967-019-02155-4
dc.identifier.urihttp://hdl.handle.net/10072/390166
dc.description.abstractBackground: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is hallmarked by a significant reduction in natural killer (NK) cell cytotoxicity, a mechanism tightly regulated by calcium (Ca2+). Interestingly, interleukin-2 (IL-2) increases NK cell cytotoxicity. Transient receptor potential melastatin 2 (TRPM2) ion channels are fundamental for Ca2+ signalling in NK cells. This pilot investigation aimed to characterise TRPM2 and CD38 surface expression in vitro on NK cells in ME/CFS patients. This investigation furthermore examined the pharmaceutical effect of 8-bromoadenosine phosphoribose (8-Br-ADPR) and N6-Benzoyladenosine-3′,5′-cyclic monophosphate (N6-Bnz-cAMP) on TRPM2 and CD38 surface expression and NK cell cytotoxicity between ME/CFS and healthy control (HC) participants. Methods: Ten ME/CFS patients (43.45 ± 12.36) and 10 HCs (43 ± 12.27) were age and sex-matched. Isolated NK cells were labelled with fluorescent antibodies to determine baseline and drug-treated TRPM2 and CD38 surface expression on NK cell subsets. Following IL-2 stimulation, NK cell cytotoxicity was measured following 8-Br-ADPR and N6-Bnz-cAMP drug treatments by flow cytometry. Results: Baseline TRPM2 and CD38 surface expression was significantly higher on NK cell subsets in ME/CFS patients compared with HCs. Post IL-2 stimulation, TRPM2 and CD38 surface expression solely decreased on the CD56DimCD16+ subset. 8-Br-ADPR treatment significantly reduced TRPM2 surface expression on the CD56BrightCD16Dim/− subset within the ME/CFS group. Baseline cell cytotoxicity was significantly reduced in ME/CFS patients, however no changes were observed post drug treatment in either group. Conclusion: Overexpression of TRPM2 on NK cells may function as a compensatory mechanism to alert a dysregulation in Ca2+ homeostasis to enhance NK cell function in ME/CFS, such as NK cell cytotoxicity. As no improvement in NK cell cytotoxicity was observed within the ME/CFS group, an impairment in the TRPM2 ion channel may be present in ME/CFS patients, resulting in alterations in [Ca2+]i mobilisation and influx, which is fundamental in driving NK cell cytotoxicity. Differential expression of TRPM2 between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in ME/CFS.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom401: 1
dc.relation.ispartofpageto401: 11
dc.relation.ispartofissue1
dc.relation.ispartofjournalJournal of Translational Medicine
dc.relation.ispartofvolume17
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchHealth sciences
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode42
dc.titleTransient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationBalinas, C; Cabanas, H; Staines, D; Marshall-Gradisnik, S, Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients, Journal of Translational Medicine, 2019, 17 (1), pp. 401: 1-401: 11
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-01-10T04:38:48Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorMarshall-Gradisnik, Sonya M.
gro.griffith.authorStaines, Donald R.


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