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Chemokine receptor inhibitor, Antileukinate, suppressed ovalbumin-induced eosinophilic inflammation in the airway
- Source :
- Cytokine. 22(5)
- Publication Year :
- 2003
-
Abstract
- Accumulating evidence suggests that eosinophils play an important role in the pathogenesis of allergic diseases. An eosinophil-active chemokine, eotaxin, and its receptor, C-C chemokine receptor 3, are particularly attractive as novel targets of immunological intervention for the disease. In this study, we examine the effects of a hexa-peptide (Ac-RRWWCR-NH 2 ), Antileukinate, which we have previously defined as a potent inhibitor of CXC chemokine receptor 1 and 2, on eotaxin in vitro and in vivo. Antileukinate inhibited the binding of 125 I-labeled human eotaxin to human eosinophils with an IC 50 of approximately 10 μM and eosinophil chemotaxis to human eotaxin was significantly inhibited by 10 μM of Antileukinate. We examined the effects of Antileukinate on eosinophil accumulation induced by intraperitoneal administration of murine eotaxin, and confirmed that Antileukinate is also active in the murine system. When Antileukinate was tested in ovalbumin-induced airway inflammation model in vivo, Antileukinate significantly inhibited eosinophil accumulation and allergen-induced increase in total protein in bronchoalveolar lavage fluids. Furthermore, Antileukinate suppressed fibrous thickening of submucosal tissue induced by chronic antigen challenge. These results suggest that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation, and that Antileukinate may be a promising tool to control allergic diseases.
- Subjects :
- Eotaxin
Chemokine CCL11
Male
Chemokine
Ovalbumin
Immunology
Guinea Pigs
Biochemistry
Chemokine receptor
Mice
Eosinophilia
medicine
Immunology and Allergy
Animals
Humans
CXC chemokine receptors
Receptor
Molecular Biology
Lung
Inflammation
biology
Dose-Response Relationship, Drug
Chemistry
Chemotaxis
Respiration
Hematology
respiratory system
Eosinophil
respiratory tract diseases
Eosinophils
medicine.anatomical_structure
Chemokines, CC
biology.protein
Eosinophil chemotaxis
Receptors, Chemokine
Oligopeptides
Subjects
Details
- ISSN :
- 10434666
- Volume :
- 22
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cytokine
- Accession number :
- edsair.doi.dedup.....8114856add07a9fd22c21497f82bfb9c