The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration
Macrophage 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 macrop...
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ndltd-VTETD-oai-vtechworks.lib.vt.edu-10919-770712020-09-29T05:38:40Z The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration Gan, Lu Biology Li, Liwu Lee, Yong Woo Lawrence, Christopher B. Hulver, Matthew W. IRAK innate immunity actin regulatory protein chemokine macrophage migration Macrophage 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. Ph. D. 2017-04-06T15:42:25Z 2017-04-06T15:42:25Z 2010-04-26 2010-05-10 2016-09-30 2010-05-24 Dissertation Text etd-05102010-061531 http://hdl.handle.net/10919/77071 http://scholar.lib.vt.edu/theses/available/etd-05102010-061531/ en_US In Copyright http://rightsstatements.org/vocab/InC/1.0/ application/pdf Virginia Tech |
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IRAK innate immunity actin regulatory protein chemokine macrophage migration |
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IRAK innate immunity actin regulatory protein chemokine macrophage migration Gan, Lu The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration |
description |
Macrophage 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. === Ph. D. |
author2 |
Biology |
author_facet |
Biology Gan, Lu |
author |
Gan, Lu |
author_sort |
Gan, Lu |
title |
The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration |
title_short |
The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration |
title_full |
The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration |
title_fullStr |
The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration |
title_full_unstemmed |
The Involvement of Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a Critical Modulator of Macrophage Migration |
title_sort |
involvement of interleukin-1 receptor-associated kinase-1 (irak-1) as a critical modulator of macrophage migration |
publisher |
Virginia Tech |
publishDate |
2017 |
url |
http://hdl.handle.net/10919/77071 http://scholar.lib.vt.edu/theses/available/etd-05102010-061531/ |
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