Improvement of Pulmonary Function by Oral Treatment with a VLA-4 Antagonist in a Mouse Asthmatic Model

• Main Authors: Gensuke Takayama (Author), Keiko Matsumoto (Author), Tomoe Taira (Author), Misato Aonuma (Author), Mika Yokoyama (Author), Yutaka Iigo (Author), Tohru Takashi (Author)
• Format: Book
• Published: Elsevier, 2013-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

We investigated in vivo efficacies of the newly synthesized VLA-4 antagonist Compound A {trans-4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid} on Ascaris antigen-induced airway inflammation and hyperresponsiveness in a murine asthmatic model. Oral administration of Compound A significantly inhibited eosinophil infiltration into BALF and airway hyperresponsiveness 48 h after the antigen challenge. Histologic analysis of the lung sections confirmed the BALF result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge, respectively. These findings clearly show that orally active Compound A has therapeutic potential for treatment of asthma. Keywords:: VLA-4, eosinophil, airway hyperresponsiveness

Item Description

1347-8613
10.1254/jphs.12198SC