ArticleThe Journal of biological chemistry2014
Blocking KV1.3 channels inhibits Th2 lymphocyte function and treats a rat model of asthma.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of potassium ion channels in chronic sinusitis.Frontiers in pharmacology · 2024Review
- Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.Nature communications · 2022Article
- The toxin mimic FS48 from the salivary gland of Xenopsylla cheopis functions as a Kv1.3 channel-blocking immunomodulator of T cell activation.The Journal of biological chemistry · 2022Article
- Synthetic polypeptide crotamine: characterization as a myotoxin and as a target of combinatorial peptides.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis.Journal of Crohn's & colitis · 2021Article
- Discovery of KMedicinal research reviews · 2021Review
- Optimization ofFrontiers in pharmacology · 2021Article
- Immunological Responses to Envenomation.Frontiers in immunology · 2021Review
- Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma.Clinical and translational allergy · 2020Article
- KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis.Arthritis research & therapy · 2019Article
- KCell communication and signaling : CCS · 2018Article
- Kv1.3 activity perturbs the homeostatic properties of astrocytes in glioma.Scientific reports · 2018Article
- Crucial role of OX40/OX40L signaling in a murine model of asthma.Molecular medicine reports · 2018Article
- Differences in ion channel phenotype and function between humans and animal models.Frontiers in bioscience (Landmark edition) · 2018Review
- Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog.Clinical immunology (Orlando, Fla.) · 2017Article
- Distribution and kinetics of the Kv1.3-blocking peptide HsTX1[R14A] in experimental rats.Scientific reports · 2017Article
- Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.Nature communications · 2017Article
- Margatoxin-bound quantum dots as a novel inhibitor of the voltage-gated ion channel Kv1.3.Journal of neurochemistry · 2017Article
- T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.PloS one · 2017Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Allergic asthma is a chronic inflammatory disease of the airways. Of the different lower airway-infiltrating immune cells that participate in asthma, T lymphocytes that produce Th2 cytokines play important roles in pathogenesis. These T cells are mainly fully differentiated CCR7(-) effector memory T (TEM) cells. Targeting TEM cells without affecting CCR7(+) naïve and central memory (TCM) cells has the potential of treating TEM-mediated diseases, such as asthma, without inducing generalized immunosuppression. The voltage-gated KV1.3 potassium channel is a target for preferential inhibition of TEM cells. Here, we investigated the effects of ShK-186, a selective KV1.3 channel blocker, for the treatment of asthma. A significant proportion of T lymphocytes in the lower airways of subjects with asthma expressed high levels of KV1.3 channels. ShK-186 inhibited the allergen-induced activation of peripheral blood T cells from those subjects. Immunization of F344 rats against ovalbumin followed by intranasal challenges with ovalbumin induced airway hyper-reactivity, which was reduced by the administration of ShK-186. ShK-186 also reduced total immune infiltrates in the bronchoalveolar lavage and number of infiltrating lymphocytes, eosinophils, and neutrophils assessed by differential counts. Rats with the ovalbumin-induced model of asthma had elevated levels of the Th2 cytokines IL-4, IL-5, and IL-13 measured by ELISA in their bronchoalveolar lavage fluids. ShK-186 administration reduced levels of IL-4 and IL-5 and induced an increase in the production of IL-10. Finally, ShK-186 inhibited the proliferation of lung-infiltrating ovalbumin-specific T cells. Our results suggest that KV1.3 channels represent effective targets for the treatment of allergic asthma.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.