Effects of VLA-1 Blockade on Experimental Inflammation in Mice
Overview
Affiliations
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.
Decrypting Integrins by Mixed-Solvent Molecular Dynamics Simulations.
Ilie I, Ehrhardt C, Caflisch A, Weitz-Schmidt G J Chem Inf Model. 2023; 63(12):3878-3891.
PMID: 37310029 PMC: 10302478. DOI: 10.1021/acs.jcim.3c00480.