Ion channels in T lymphocytes: An update on facts, mechanisms and therapeutic targeting in autoimmune diseases

Varga, Zoltán; Hajdú, Péter; Panyi, György

doi:10.1016/j.imlet.2009.12.015

Cited by 47 publications

(39 citation statements)

References 74 publications

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“…Also, the Blong-term effect^of modified operation of ion channels could be traced with the proliferation assay: SLOS cells tended to divide at a lower rate compared to control T cells, a phenomenon which was clearly shown for Kv1.3 inhibitors [10,63]. The Ca 2+ -signaling-linked activation of T lymphocytes is a classic example of the interplay of ion channels, transporters, and signaling molecules (see above), reviewed in [22,64]. Even though the sterol sensitivity of Kv1.3 is a potential mechanism for the reduced T cell activation/proliferation, we cannot exclude that the altered lipid milieu in SLOS affects other transporters and/or signaling molecules, which contribute to the altered T cell function in SLOS.…”

Section: Discussionmentioning

confidence: 99%

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

Balajthy

Somodi

Pethő

et al. 2016

Pflugers Arch - Eur J Physiol

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In vitro manipulation of membrane sterol level affects the regulation of ion channels and consequently certain cellular functions; however, a comprehensive study that confirms the pathophysiological significance of these results is missing. The malfunction of 7-dehydrocholesterol (7DHC) reductase in Smith-Lemli-Opitz syndrome (SLOS) leads to the elevation of the 7-dehydrocholesterol level in the plasma membrane. T lymphocytes were isolated from SLOS patients to assess the effect of the in vivo altered membrane sterol composition on the operation of the voltage-gated Kv1.3 channel and the ion channel-dependent mitogenic responses. We found that the kinetic and equilibrium parameters of Kv1.3 activation changed in SLOS cells. Identical changes in Kv1.3 operation were observed when control/healthy T cells were loaded with 7DHC. Removal of the putative sterol binding sites on Kv1.3 resulted in a phenotype that was not influenced by the elevation in membrane sterol level. Functional assays exhibited impaired activation and proliferation rate of T cells probably partially due to the modified Kv1.3 operation. We concluded that the altered membrane sterol composition hindered the operation of Kv1.3 as well as the ion channel-controlled T cell functions.

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Section: Discussionmentioning

confidence: 99%

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

Balajthy

Somodi

Pethő

et al. 2016

Pflugers Arch - Eur J Physiol

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“…05.002 et al, 2006) or obesity and insulin resistance (Upadhyay et al, 2013). K þ channels play a key role in the regulation of the membrane potential of excitable and non-excitable cells (Abbott, 2006;Korn and Trapani, 2005;Varga et al, 2010Varga et al, , 2011. Kv1.3 is a voltage-gated K þ channel, which is expressed in a variety of cells and tissues e.g.…”

Section: Toxicon XXX (2014) 1e11mentioning

confidence: 99%

Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels

Bartók

Tóth

Somodi

et al. 2014

Toxicon

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“…Another pathway with differential gene expression was the calcium signalling pathway. Calcium is involved many biological and immune system functions such as T lymphocyte activation, 18 the immunological synapse (IS) between T cells and antigen-presenting cells 19 and phagocytosis. 20 However, the depression of the cAMP and Ca pathway genes is difficult to interpret as almost every cell uses these pathways at the initiation of different signalling pathways and this effect should be elucidated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: A pilot study

et al. 2012

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Introduction: It remains unknown why some intubated patients remain infection-free while others develop tracheobronchitis (VAT) or pneumonia (VAP).Objective: To identify and compare VAP/VAT gene expression ''signatures'' using genome-wide oligonucleotide microarrays. Material and methods: A prospective translational study of gene expression profiles of VAP and VAT groups was carried out, establishing comparisons in both pre-infection and infection phases. Pathway and functional analyses were performed with Ingenuity Pathway Analysis (IPA). Data analysis and hierarchical clustering of the genes involved in the signalling pathways expressed differentially in the two groups were performed with GeneSpring GX 11.0. Results: Eight patients developing respiratory infections (3 VAP and 5 VAT) after 4 days of mechanical ventilation were assessed. Comparison of gene expression profiles in the preinfection period revealed 5595 genes expressed differentially between VAP and VAT (p < 0.01, fold change >2). Comparative IPA analysis identified a significant depression of the complement system signalling pathway in the VAP group, affecting the classical pathway along with the final common pathway (p < 0.05). In addition, the cAMP and calcium signalling pathways were also significantly depressed in the VAP group during the pre-infection phase also. Conclusion: Intubated patients complicated with pneumonia developed immune impairment in the pre-infection period, manifesting as a relatively lower expression of genes involved in the complement system that differed from patients developing tracheobronchitis. These findings suggest that a significant proportion of VAP episodes cannot be prevented, but might be treatable through pre-emptive therapy. PALABRAS CLAVE traqueobronquitis (TAV) o neumonía (NAV).Objetivo: Identificar y comparar los patrones de la expresión genética de la NAV/TAV usando micromatrices multigénicas oligonucleotídicas. Material y métodos: Se realizó un estudio aplicado prospectivo de los patrones de la expresión genética de los grupos con NAV y TAV, estableciendo comparaciones tanto en la fase previa a la infección como en la fase infecciosa. Se realizaron análisis de vías y funcionales con Ingenuity Pathway (IPA). Los análisis de datos y el agrupamiento jerárquico de los genes implicados en las vías de señalización expresados de forma diferenciada en ambos grupos se realizaron con GeneSpring GX 11.0. Resultados: Se evaluaron ocho pacientes que presentaron infecciones respiratorias (3 NAV y 5 TAV) después de 4 días con la ventilación mecánica. La comparación de los perfiles de la expresión genética durante el período previo a la infección reveló 5.595 genes expresados de forma diferenciada entre la NAV y la TAV (p < 0,01, cambio múltiplo > 2). Los análisis comparativos de los IPA identificaron una depresión importante de la vía de señalización del sistema del complemento en el grupo con NAV, que afectó a la vía clásica además de a la vía común final (p < 0,05). Por otra parte, el monofosfato cíclico de...

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Ion channels in T lymphocytes: An update on facts, mechanisms and therapeutic targeting in autoimmune diseases

Cited by 47 publications

References 74 publications

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels

Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: A pilot study

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