کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3202279 | 1201970 | 2009 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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 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](/preview/png/3202279.png)
BackgroundEosinophil 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.ObjectiveWe sought to determine whether additional signaling molecules/pathways are critically involved in IL-5–mediated eosinophil survival.MethodsEosinophil 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.ResultsAlthough 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.ConclusionsPim-1, but not PI3K, plays a major role in IL-5–mediated antiapoptotic signaling in eosinophils.
Journal: Journal of Allergy and Clinical Immunology - Volume 123, Issue 3, March 2009, Pages 603–611