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Role of CCR5 in the pathogenesis of IL-13-induced inflammation and remodeling.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Apr 15; Vol. 176 (8), pp. 4968-78. - Publication Year :
- 2006
-
Abstract
- IL-13 is a major effector at sites of Th2 inflammation and tissue remodeling. In these locations, it frequently coexists with the CCR5 chemokine receptor and its ligands MIP-1alpha/CCL3 and MIP-1beta/CCL4. We hypothesized that CCR5 induction and activation play important roles in the pathogenesis of IL-13-induced tissue responses. To test this hypothesis, we evaluated the effects of IL-13 on the expression of CCR5 in the murine lung. We also compared the effects of lung-targeted transgenic IL-13 in mice treated with anti-CCR5 or an Ab control and mice with wild-type or null CCR5 loci. These studies demonstrate that IL-13 is a potent stimulator of epithelial cell CCR5 expression. They also demonstrate that CCR5 neutralization or a deficiency of CCR5 significantly decreases IL-13-induced inflammation, alveolar remodeling, structural and inflammatory cell apoptosis, and respiratory failure and death. Lastly, these studies provide mechanistic insights by demonstrating that CCR5 is required for optimal IL-13 stimulation of select chemokines (MIP-1alpha/CCL3, MIP-1beta/CCL4, MCP-1/CCL-2), matrix metalloproteinase-9 and cell death regulators (Fas, TNF, TNFR1, TNFR2, Bid), optimal IL-13 inhibition of alpha1-antitrypsin, and IL-13-induction of and activation of caspases-3, -8, and-9. Collectively, these studies demonstrate that CCR5 plays a critical role in the pathogenesis of IL-13-induced inflammation and tissue remodeling.
- Subjects :
- Animals
Base Sequence
DNA genetics
DNA Damage
Inflammation immunology
Inflammation pathology
Interleukin-13 antagonists & inhibitors
Interleukin-13 genetics
Lung immunology
Lung pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neutralization Tests
Peptide Hydrolases metabolism
Receptors, CCR5 deficiency
Receptors, CCR5 genetics
Signal Transduction
Inflammation etiology
Interleukin-13 physiology
Receptors, CCR5 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 176
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 16585593
- Full Text :
- https://doi.org/10.4049/jimmunol.176.8.4968