Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade initiated by IL-5 in eosinophils - 15/08/11
Abstract |
Background |
Eosinophil differentiation, activation, and survival are largely regulated by IL-5. IL-5–mediated transmembrane signal transduction involves both Lyn–mitogen-activated protein kinases and Janus kinase 2–signal transducer and activator of transcription pathways.
Objective |
We sought to determine whether additional signaling molecules/pathways are critically involved in IL-5–mediated eosinophil survival.
Methods |
Eosinophil survival and apoptosis were measured in the presence and absence of IL-5 and defined pharmacologic inhibitors in vitro. The specific role of the serine/threonine kinase proviral integration site for Moloney murine leukemia virus (Pim) 1 was tested by using HIV–transactivator of transcription fusion proteins containing wild-type Pim-1 or a dominant-negative form of Pim-1. The expression of Pim-1 in eosinophils was analyzed by means of immunoblotting and immunofluorescence.
Results |
Although pharmacologic inhibition of phosphatidylinositol-3 kinase (PI3K) by LY294002, wortmannin, or the selective PI3K p110δ isoform inhibitor IC87114 was successful in each case, only LY294002 blocked increased IL-5–mediated eosinophil survival. This suggested that LY294002 inhibited another kinase that is critically involved in this process in addition to PI3K. Indeed, Pim-1 was rapidly and strongly expressed in eosinophils after IL-5 stimulation in vitro and readily detected in eosinophils under inflammatory conditions in vivo. Moreover, by using specific protein transfer, we identified Pim-1 as a critical element in IL-5–mediated antiapoptotic signaling in eosinophils.
Conclusions |
Pim-1, but not PI3K, plays a major role in IL-5–mediated antiapoptotic signaling in eosinophils.
Le texte complet de cet article est disponible en PDF.Key words : Apoptosis, eosinophils, inflammation, IL-5, phosphatidylinositol-3 kinase, proviral integration site for Moloney murine leukemia virus
Abbreviations used : DN, ECP, GSK, HA, Jak, Pim, PI3K, PMB, STAT, TAT, TBS, WT
Plan
Supported by grants from the Swiss National Science Foundation (310000-107526 and 320000-116304) and the OPO Foundation, Zurich, Switzerland. |
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Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 123 - N° 3
P. 603-611 - mars 2009 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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