title: A single injection of a sustained-release prostacyclin analog (ONO-1301MS) suppresses airway inflammation and remodeling in a chronic house dust mite-induced asthma model.
abstract: ONO-1301, a novel prostacyclin agonist with thromboxane A2 synthase inhibitory activity, is a useful agent for ameliorating airway allergic inflammation; however, its short-action feature implies a requirement for the frequent administration of this drug. Therefore, we investigated the effects of ONO-1301-loaded poly (d,l-lactic-co-glycolic acid) microspheres (ONO-1301MS; to release ONO-1301 for 3 weeks) on the airway inflammation and remodeling in chronic house dust mite (HDM)-induced model. Balb/c mice were exposed to an HDM extract intranasally for 5 days/week for 5 consecutive weeks. The mice received a single subcutaneous injection of ONO-1301MS or vehicle after 3 weeks of HDM exposure, followed by 2 additional weeks of HDM exposure. Forty-eight hours after the last HDM exposure, airway hyperresponsiveness to methacholine was assessed and bronchoalveolar lavage was performed. Lung specimens were excised and stained to check for goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal fibrosis. Mice receiving ONO-1301MS showed significantly lower airway hyperresponsiveness, airway eosinophilia, and induced T helper 2 cytokine production compared with mice receiving the vehicle. Histological findings such as goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal fibrosis were decreased in ONO-1301MS-treated mice compared with vehicle-treated mice. A single administration of ONO-1301MS achieved sustained elevation of its circulating level for 3 weeks. These data suggest that a single administration of ONO-1301MS may suppress airway hyperresponsiveness, airway allergic inflammation, and development of airway remodeling in chronic HDM-induced asthma model. This agent may be effective as an anti-inflammatory and remodeling drug in the practical treatment of asthma.
authors.affiliation: Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kagamu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Shima
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kawakami
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Toshiki
authors.initials: T
authors.lastname: Furukawa
authors.forename: Takuro
authors.initials: T
authors.lastname: Sakagami
authors.forename: Takashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Masami
authors.initials: M
authors.lastname: Narita
authors.forename: Eiichi
authors.initials: E
authors.lastname: Suzuki
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D007267:Injections; D051379:Mice; D008863:Microspheres; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D039981:Pyroglyphidae; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology
chemical_list: D003692:Delayed-Action Preparations; D011725:Pyridines; C105488:ONO 1301
keywords: Airway remodeling; Bronchial asthma; House dust mite (HDM); Microsphere; ONO-1301; Prostacyclin