Idioma:

Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma

Koshy, Shyny ; Huq, Redwan ; Tanner, Mark R. ; Atik, Mustafa A. ; Porter, Paul C. ; Khan, Fatima S. ; Pennington, Michael W. ; Hanania, Nicola A. ; Corry, David B. ; Beeton, Christine

The Journal of biological chemistry, 2014-05, Vol.289 (18), p.12623-12632 [Revista revisada por pares]

United States: Elsevier Inc

Texto completo disponible

Citas Citado por

Acciones

Título:
Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma
Autor: Koshy, Shyny ; Huq, Redwan ; Tanner, Mark R. ; Atik, Mustafa A. ; Porter, Paul C. ; Khan, Fatima S. ; Pennington, Michael W. ; Hanania, Nicola A. ; Corry, David B. ; Beeton, Christine
Materias: Adult ; Airway Inflammation ; Allergy ; Animal Models ; Animals ; Asthma ; Asthma - immunology ; Asthma - metabolism ; Asthma - prevention & control ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchoalveolar Lavage Fluid - immunology ; Cellular Immune Response ; Disease Models, Animal ; Female ; Flow Cytometry ; Humans ; Immunologic Memory - drug effects ; Immunologic Memory - immunology ; Interleukin-10 - immunology ; Interleukin-10 - metabolism ; Interleukin-13 - immunology ; Interleukin-13 - metabolism ; Interleukin-4 - immunology ; Interleukin-4 - metabolism ; Interleukin-5 - immunology ; Interleukin-5 - metabolism ; KCNA3 ; KV1.3 ; Kv1.3 Potassium Channel - antagonists & inhibitors ; Kv1.3 Potassium Channel - immunology ; Kv1.3 Potassium Channel - metabolism ; Male ; Middle Aged ; Molecular Bases of Disease ; Ovalbumin - immunology ; Potassium Channel Blockers - immunology ; Potassium Channel Blockers - pharmacology ; Potassium Channels ; Proteins - immunology ; Proteins - pharmacology ; Rats ; Rats, Inbred F344 ; T Lymphocyte ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Th2 Cells - drug effects ; Th2 Cells - immunology ; Th2 Cells - metabolism ; Therapy ; Young Adult
Es parte de: The Journal of biological chemistry, 2014-05, Vol.289 (18), p.12623-12632
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Supported in part by Howard Hughes Medical Institutes Med into Grad Initiative and National Institutes of Health Award T32 GM088129.
Supported by American Lung Association Fellowship RT-197120-N.
Descripción: 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. CCR7− effector memory T lymphocytes are major players in lung inflammation that characterizes allergic asthma. Blocking KV1.3 channels reduced the severity of an ovalbumin-induced model of asthma in rats. KV1.3 channels are attractive targets for immunomodulation and the treatment of allergic asthma. Selective KV1.3 channel blockers may prove beneficial in the treatment of asthma.
Editor: United States: Elsevier Inc
Idioma: Inglés

Enlaces

View this record in MEDLINE/PubMed

Volver a la lista de resultados

Anterior Resultado 11 Siguiente Ir a la siguiente página

Realización: Logos de Redes Sociales:

Blocking KV1.3 Channels Inhibits Th2 Lymphocyte Function and Treats a Rat Model of Asthma

Koshy, Shyny ; Huq, Redwan ; Tanner, Mark R. ; Atik, Mustafa A. ; Porter, Paul C. ; Khan, Fatima S. ; Pennington, Michael W. ; Hanania, Nicola A. ; Corry, David B. ; Beeton, Christine

United States: Elsevier Inc

Buscando en bases de datos remotas, por favor espere