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IL-4R, a New Member that Associates with Syk Kinase: Implication in IL-4-Induced Human Neutrophil Functions¹

Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, Institut national de la recherche scientifique-Institut Armand-Frappier, Laval, Quebec, Canada

Although Syk has been reported to be associated with IL-2R and IL-15R in some hematopoietic cells, its association has never been investigated in the IL-4/IL-4R system. In this study, we demonstrate for the first time that Syk is constitutively associated with IL-4R in human polymorphonuclear neutrophils (PMNs) and that IL-4 stimulation increases the amount of Syk associated with IL-4R. Moreover, upon IL-4 treatment, a pool of Syk associated with IL-4R is phosphorylated. We also report that such association is not unique to PMNs because Syk associates with IL-4R in Raji and in PBMC cells. Stimulation of PMNs by IL-4 increased the amount of Syk associated with PLC-2, pAkt, and -tubulin. Pretreatment of cells with the Syk-selective inhibitor piceatannol or Syk inhibitor II, significantly inhibited the ability of IL-4 to enhance phagocytosis and cell adhesion and to delay apoptosis, and these results correlate with the ability of piceatannol to reduce Syk activation and its association with IL-4R. Down-regulation of Syk by antisense techniques demonstrates the importance of Syk in the antiapoptotic effect of IL-4. We conclude that association of Syk to IL-4R is of biological significance and that IL-4R is a new candidate to be added to the few cytokine receptor components which associate with Syk.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was partly supported by the Canadian Institutes of Health Research (CIHR; MOP-89534) and Fonds de la Recherche en Santé du Québec (FRSQ). J.E. holds a Fondation Armand-Frappier Post-doctoral award and D.G. is a Scholar from FRSQ.

² Address correspondence and reprint requests to Denis Girard, Institut national de la recherche scientifique-Institut Armand-Frappier, 531 boul. des Prairies, Laval, Quebec, Canada. E-mail address: denis.girard{at}iaf.inrs.ca

³ Abbreviations used in this paper: PMN, polymorphonuclear neutrophil; ASO, antisense oligonucleotide; scr-ODN, scrambled oligonucleotide.