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Closed Access item Chemokine receptor CCR7 induces intracellular signaling that inhibits apoptosis of mature dendritic cells

Authors:Sánchez-Sánchez, Noelia
Riol-Blanco, Lorena
Rosa, Gonzalo de la
Puig-Kröger, Amaya
García-Bordas, Julio
Martín, Daniel
Longo, Natividad
Cuadrado, Antonio
Cabañas, Carlos
Corbí, Angel L.
Sánchez-Mateos, Paloma
Rodríguez-Fernández, José Luis
Keywords:CCR7 expression, serum-deprived DCs, membrane phosphatidylserine exposure, phosphatidylinositol 3'-kinase/Akt1 (PI3K/Akt1)
Issue Date:1-Aug-2004
Publisher:American Society of Hematology
Citation:Blood 104:619-625 (2004)
Abstract:Acquisition of CCR7 expression is an important phenotype change during dendritic cell (DC) maturation that endows these cells with the capability to migrate to lymph nodes. We have analyzed the possible role of CCR7 on the regulation of the survival of DCs. Stimulation with CCR7 ligands CCL19 and CCL21 inhibits apoptotic hallmarks of serum-deprived DCs, including membrane phosphatidylserine exposure, loss of mitochondria membrane potential, increased membrane blebs, and nuclear changes. Both chemokines induced a rapid activation of phosphatidylinositol 3'-kinase/Akt1 (PI3K/Akt1), with a prolonged and persistent activation of Akt1. Interference with PI3K, Gi, or G protein γ subunits abrogated the effects of the chemokines on Akt1 activation and on survival. In contrast, inhibition of extracellular signal-related kinase 1/2 (Erk1/2), p38, or c-Jun N-terminal kinase (JNK) was ineffective. Nuclear factor–κB (NFκB) was involved in the antiapoptotic effects of chemokines because inhibition of NFκB blunted the effects of CCL19 and CCL21 on survival. Furthermore, chemokines induced down-regulation of the NFκB inhibitor IκB, an increase of NFκB DNA-binding capability, and translocation of the NFκB subunit p65 to the nucleus. In summary, in addition to its well-established role in chemotaxis, we show that CCR7 also induces antiapoptotic signaling in mature DCs.
Description:6 Figures. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. section 1734.
Publisher version (URL):http://bloodjournal.hematologylibrary.org/content/104/3/619.abstract
URI:http://hdl.handle.net/10261/41634
ISSN:0006-4971
E-ISSNmetadata.dc.identifier.doi = DOI:1528-0020
???metadata.dc.identifier.doi???:10.1182/blood-2003-11-3943
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