title: Dihydropyridine receptor blockade in the treatment of asthma.
abstract: Asthma is a chronic airway disease resulting from inappropriate Th2-cell biased activation. Interleukin (IL)-4, IL-5 and IL-13 produced by Th2 cells contribute to the inflammatory process. Attempts for inhibiting interleukin-4 or IL-5 gave disappointing results. The simultaneous inhibition of several Th2-cytokines could be a more promising issue. Several arguments support the concept that Th2-cells express selective markers that could be targeted in asthma. Our group showed that Th2-cells selectively up-regulated dihydropyridine-sensitive Ca(2+) (DHP-Ca) channels essential for Ca(2+) signaling and type-2 cytokine production. Indeed, DHP-Ca antagonist effectively prevented or even reverted airway inflammation, airway remodeling and airway hyperresponsiveness in experimental models of asthma. Although it remains to be formally demonstrated that human lung infiltrating T-lymphocytes in asthmatic patients express DHP- Ca(2+) channels, we hypothesize that targeting DHP-Ca channels in T-lymphocytes could represent an efficient strategy in the treatment of asthma.This review article also discussed patents relevant to the field.
authors.affiliation: INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France. Lucette.Pelletier@toulouse.inserm.fr
authors.forename: Lucette
authors.initials: L
authors.lastname: Pelletier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Guéry
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D010330:Patents as Topic; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000276:immunology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016207:Cytokines