Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients
| العنوان: | Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients |
|---|---|
| المؤلفون: | Hélène Cabanas, Donald Staines, Sonya Marshall-Gradisnik, Cassandra Balinas |
| المصدر: | Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-11 (2019) Journal of Translational Medicine |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Interleukin 2, Adult, Cytotoxicity, Immunologic, Male, Encephalomyelitis, Cell, TRPM Cation Channels, lcsh:Medicine, Stimulation, CD38, General Biochemistry, Genetics and Molecular Biology, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, TRPM2, Adenosine diphosphate ribose, Cyclic ADP-Ribose, Fatigue Syndrome, Chronic, biology, medicine.diagnostic_test, Chemistry, Research, lcsh:R, General Medicine, medicine.disease, ADP-ribosyl Cyclase 1, Killer Cells, Natural, Transient receptor potential melastatin 2, 030104 developmental biology, medicine.anatomical_structure, Myalgic encephalomyelitis/chronic fatigue syndrome, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Interleukin-2, Natural killer cells, Female, Calcium, Antibody, medicine.drug |
| الوصف: | Background 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. |
| اللغة: | English |
| تدمد: | 1479-5876 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9e60c5262fe2d0a51f9918ac96c8c52Test https://doaj.org/article/8cbd2da5d83c47c881241e44a3db55d5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d9e60c5262fe2d0a51f9918ac96c8c52 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14795876 |
|---|