Abstract |
CC chemokine receptor 1 (CCR1) represents a promising target in chronic airway inflammation and remodeling due to fungus-associated allergic asthma. The present study addressed the therapeutic effect of a nonpeptide CCR1 antagonist, BX-471, in a model of chronic fungal asthma induced by Aspergillus fumigatus conidia. BX-471 treatment of isolated macrophages inhibited CCL22 and TNF-alpha and promoted IL-10 release. BX-471 also increased toll like receptor-9 (TLR9) and decreased TLR2 and TLR6 expression in these cells. When administered daily by intraperitoneal injection, from days 15 to 30 after the initiation of chronic fungal asthma, BX-471 (3, 10, or 30 mg kg(-1)) dose-dependently reduced airway inflammation, hyper-responsiveness, and remodeling at day 30 after conidia challenge. The maximal therapeutic effect was observed at the 10 mg kg(-1) dose. In summary, the therapeutic administration of BX-471 significantly attenuated experimental fungal asthma via its effects on both innate and adaptive immune processes.
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Authors | Kristin J Carpenter, Jillian L Ewing, Jane M Schuh, Traci L Ness, Steven L Kunkel, Monica Aparici, Montserrat Miralpeix, Cory M Hogaboam |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 145
Issue 8
Pg. 1160-72
(Aug 2005)
ISSN: 0007-1188 [Print] England |
PMID | 15951834
(Publication Type: Journal Article)
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Chemical References |
- Ccr1 protein, mouse
- Phenylurea Compounds
- Piperidines
- Receptors, CCR1
- Receptors, Chemokine
- BX 471
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Topics |
- Animals
- Aspergillosis
(drug therapy, immunology, microbiology)
- Aspergillus fumigatus
(immunology)
- Asthma
(drug therapy, immunology, microbiology)
- Chronic Disease
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Immunity, Innate
(drug effects)
- Macrophages, Peritoneal
(drug effects, metabolism)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred CBA
- Phenylurea Compounds
(therapeutic use)
- Piperidines
(therapeutic use)
- Receptors, CCR1
- Receptors, Chemokine
(antagonists & inhibitors)
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