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Kobe J Med Sci. 2016 Jul 5;62(2):E27-37.

Effects of VLA-1 Blockade on Experimental Inflammation in Mice.

Author information

1
Department of Integrated Drug Discovery Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
2
Pharmacology Research Laboratories I, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan.
3
Department of Hospital Pharmacy, Kobe University School of Medicine, Kobe, Japan.

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.

KEYWORDS:

Airway inflammation; Arthritis; Dermatitis; Ha31/8; Inflammation; VLA-1

PMID:
27578034
PMCID:
PMC5425133
[Indexed for MEDLINE]
Free PMC Article

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