Virginia Tech
The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration
Abstract
dc:description.abstractMacrophage migration, an essential component of many biological processes and pathologic conditions, is mediated by integrated cellular signaling processes and cytoskeleton rearrangement. Recent advances indicate that the innate immunity signaling process plays a key role in the regulation of macrophage migration. Furthermore, our lab has provided evidence demonstrating the involvement of a key innate immunity signaling kinase, IRAK-1, as a critical modulator of murine macrophage migration. Macrophage migration induced by a potent PKC activator, phorbol 12-myristate 13-acetate (PMA), or lipopolysaccharide (LPS) was significantly decreased in IRAK-1-/- murine macrophages compared with wild type cells. Mechanistically, we first demonstrated that IRAK-1 works downstream of PKCε and directly binds to VASP, a cytoskeleton regulatory protein, to regulate PMA-induced macrophage migration. Secondly, we proved that IRAK-1 is required for LPS-induced macrophage migration and expression of MCP-1, a chemotactic cytokine for macrophages, via transcription factor C/EBPδ instead of NFκB. IRAK-1 binds directly to IKKε and inhibition or knock-down of IKKε results in a significant decrease in C/EBPδ expression and MCP-1 mRNA expression. Lastly, we identified the direct association between IRAK-1 and Rac1, a member of the Rac subfamily in the Rho family of GTPases. These finding further confirmed the essential role of IRAK-1 during macrophage migration. Our research provides a novel facet regarding the molecular signaling processes regulating macrophage migration.
Degree
thesis:*- Name thesis:degree_name
- Ph. D.
- Level thesis:degree_level
- doctoral
- Discipline thesis:degree_discipline
- Biology
- Department dc:contributor.department
- Biology
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 2010
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Gan, Lu
- Chair dc:contributor.committeechair
-
- Li, Liwu
- Committee members dc:contributor.committeemember
-
- Lee, Yong Woo
- Lawrence, Christopher B.
- Hulver, Matthew W.
Subjects
dc:subject × 5Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
- Language dc:language.iso
- en_US
Identifiers
dc:identifier.*- Dc Identifier Other
- etd-05102010-061531
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/77071