Inhibition of endotoxin- and antigen-induced airway inflammation by fudosteine, a mucoactive agent.

Abstract

We evaluated the effect of a mucoactive agent (-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid (fudosteine), on airway inflammation using endotoxin- and antigen-induced models. Time courses of growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) production, neutrophil migration and goblet cell hyperplasia were examined in endotoxin-induced rat airway inflammation. GRO/CINC-1 in bronchoalveolar lavage fluid (BALF) increased in response to intratracheal instillation of endotoxin and peaked within 4 h. Neutrophils in BALF and goblet cells on trachea peaked 24 and 96 h after endotoxin instillation, respectively. Fudosteine significantly inhibited increases in GRO/CINC-1 at 10-100 mg/kg, and neutrophils and goblet cells at 30 and 100 mg/kg. These results suggest that inflammatory events including neutrophil chemoattractant production and neutrophil migration play important roles for goblet cell hyperplasia in endotoxin-induced airway inflammation, and fudosteine inhibits goblet cell hyperplasia by inhibiting GRO/CINC-1 production and/or neutrophil migration. Furthermore, fudosteine (100 mg/kg) inhibited ovalbumin-induced eosinophil infiltration into BALF, suggesting it attenuates asthmatic inflammation.

• Authors: H Komatsu, S Yamaguchi, N Komorita, K Goto, S Takagi, H Ochi, T Okumoto
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 18 Issue 2 Pg. 121-7 ( 2005) ISSN: 1094-5539 [Print] England
• PMID: 15649854 (Publication Type: Journal Article)

Chemical References

• Chemokine CXCL1
• Chemokines, CXC
• Cxcl1 protein, mouse
• Expectorants
• Intercellular Signaling Peptides and Proteins
• Leukotriene B4
• Cystine
• fudosteine

Topics

• Animals
• Chemokine CXCL1
• Chemokines, CXC (antagonists & inhibitors, biosynthesis)
• Cystine (analogs & derivatives, pharmacology)
• Expectorants (pharmacology)
• Goblet Cells (metabolism)
• Intercellular Signaling Peptides and Proteins (biosynthesis)
• Leukotriene B4 (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Models, Animal
• Neutrophils (metabolism)
• Pulmonary Eosinophilia (metabolism)
• Rats
• Rats, Inbred F344
• Respiratory Mucosa (drug effects, metabolism)
• Trachea (drug effects, metabolism)