title: Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases.
abstract: T lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes. Patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies further revealed the clinically relevant relationship between the channel expression and the development of chronic respiratory diseases, in which chronic inflammation or the overstimulation of cellular immunity in the airways is responsible for the pathogenesis. In chronic respiratory diseases, such as chronic obstructive pulmonary disease, asthma, diffuse panbronchiolitis and cystic fibrosis, in addition to the supportive management for the symptoms, the anti-inflammatory effects of macrolide antibiotics were shown to be effective against the over-activation or proliferation of T lymphocytes. Recently, we provided physiological and pharmacological evidence that macrolide antibiotics, together with calcium channel blockers, HMG-CoA reductase inhibitors, and nonsteroidal anti-inflammatory drugs, effectively suppress the Kv1.3-channel currents in lymphocytes, and thus exert anti-inflammatory or immunomodulatory effects. In this review article, based on the findings obtained from recent in vivo and in vitro studies, we address the novel therapeutic implications of targeting the lymphocyte Kv1.3-channels for the treatment of chronic or acute respiratory diseases.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Miyagi, Japan. kazaitsu@med.tohoku.ac.jp.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tamada
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D012140:Respiratory Tract Diseases / Q000188:drug therapy*
chemical_list: D051664:Kv1.3 Potassium Channel; D018942:Macrolides; D026902:Potassium Channel Blockers
keywords: Acute respiratory infection; Chronic respiratory diseases; Delayed rectifier K+-channels (Kv1.3); Immunomodulatory effects; Kv1.3-channels inhibitors; Macrolide antibiotics; T lymphocytes