Cyclooxygenase-2 deficiency in macrophages leads to defective p110γ PI3K signaling and impairs cell, adhesion and migration
| العنوان: | Cyclooxygenase-2 deficiency in macrophages leads to defective p110γ PI3K signaling and impairs cell, adhesion and migration |
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| المؤلفون: | Miguel A. Iñiguez, Manuel D. Díaz-Muñoz, Inés C. Osma-García, Manuel Fresno |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | American Association of Immunologists, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | rac1 GTP-Binding Protein, Mice, 129 Strain, Immunology, CDC42, Mice, Phosphatidylinositol 3-Kinases, Chemokine receptor, Cell Adhesion, Animals, Class Ib Phosphatidylinositol 3-Kinase, Immunology and Allergy, Macrophage, cdc42 GTP-Binding Protein, Cell adhesion, Cells, Cultured, PI3K/AKT/mTOR pathway, Paxillin, Mice, Knockout, biology, Models, Immunological, Cell biology, Mice, Inbred C57BL, Fibronectin, Integrin alpha M, Cyclooxygenase 2, Cell Migration Inhibition, Macrophages, Peritoneal, biology.protein, Signal Transduction |
| الوصف: | Cyclooxygenase (Cox)-2 dependent PGs modulate several functions in many pathophysiological processes, including migration of immune cells. In this study, we addressed the role of Cox-2 in macrophage migration by using in vivo and in vitro models. Upon thioglycolate challenge, CD11b+ F4/80 + macrophages showed a diminished ability to migrate to the peritoneal cavity in cox-2-/- mice. In vivo migration of cox-2 -/- macrophages from the peritoneal cavity to lymph nodes, as well as cell adhesion to the mesothelium, was reduced in response to LPS. In vitro migration of cox-2-/- macrophages toward MCP-1, RANTES, MIP-1α, or MIP-1β, as well as cell adhesion to ICAM-1 or fibronectin, was impaired. Defects in cell migration were not due to changes in chemokine receptor expression. Remarkably, cox-2-/- macrophages showed a deficiency in focal adhesion formation, with reduced phosphorylation of paxillin (Tyr188). Interestingly, expression of the p110γ catalytic subunit of PI3K was severely reduced in the absence of Cox-2, leading to defective Akt phosphorylation, as well as cdc42 and Rac-1 activation. Our results indicate that the paxillin/p110γ-PI3K/Cdc42/Rac1 axis is defective in cox-2-/- macrophages, which results in impaired cell adhesion and migration. Copyright © 2013 by The American Association. Comunidad Autonoma de Madrid (S2010/BMD-2332); the Cardiovascular Red Temática de Investigacion en Enfermedades Cardiovasculares and Red de Investigacion Cooperativa en Enfermedades Tropicales Networks of the Instituto de Salud Carlos III (RD06/0014/1013 and RD06/0021/0016); the European Union (EICOSANOX LSH-CT-2004-005033); Ministerio de Ciencia e Innovacion (SAF2007-61716 and SAF2010-18733) and BFU2010-21055 and SAF2011-23971); Fondo de Investigacion Sanitaria; Fundacion Ramon Areces |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0995cf1f61c78b7d49370252058c83aaTest http://hdl.handle.net/10261/95733Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0995cf1f61c78b7d49370252058c83aa |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |