title: Effects of VLA-1 Blockade on Experimental Inflammation in Mice.
abstract: VLA-1 (very late antigen-1) is implicated in recruitment, retention and activation of leukocytes and its blockade has been referred as a potential target of new drug discovery to address unmet medical needs in inflammatory disease area. In the present study, we investigate the effects of an anti-murine CD49a (integrin α subunit of VLA-1) monoclonal antibody (Ha31/8) on various experimental models of inflammatory diseases in mice. Pretreatment with Ha31/8 at an intraperitoneal dose of 250 µg significantly (P<0.01) reduced arthritic symptoms and joint tissue damage in mice with type II collagen-induced arthritis. In addition, Ha31/8 at an intraperitoneal dose of 100 µg significantly (P<0.01) inhibited airway inflammatory cell infiltration induced by repeated exposure to cigarette smoke. In contrast, Ha31/8 failed to inhibit oxazolone-induced chronic dermatitis and OVA-induced airway hyperresponsiveness at an intraperitoneal dose of 100 µg. These results show that VLA-1 is involved, at least partly, in the pathogenesis of type II collagen-induced arthritis and cigarette smoke-induced airway inflammatory cell infiltration in mice, indicating the therapeutic potential of VLA-1 blockade against rheumatoid arthritis and chronic occlusive pulmonary disease.
authors: Department of Integrated Drug Discovery Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.|Pharmacology Research Laboratories I, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan.
authors: Ryuichi
authors: R
authors: Totsuka
authors: Pharmacology Research Laboratories I, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan.
authors: Takaaki
authors: T
authors: Kondo
authors: Pharmacology Research Laboratories I, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan.
authors: Shigeki
authors: S
authors: Matsubara
authors: Department of Hospital Pharmacy, Kobe University School of Medicine, Kobe, Japan.
authors: Midori
authors: M
authors: Hirai
authors: Department of Integrated Drug Discovery Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Yoichi
authors: Y
authors: Kurebayashi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control; D001249:Asthma / Q000276:immunology / Q000517:prevention & control; D003872:Dermatitis / Q000276:immunology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control; D012907:Smoking / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D039222:Integrin alpha1beta1
keywords: Airway inflammation; Arthritis; Dermatitis; Ha31/8; Inflammation; VLA-1