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Molecular mechanisms involved in interleukin‐4‐induced human neutrophils: expression and regulation of suppressor of cytokine signaling
Author(s) -
Ratthé Claude,
Pelletier Martin,
Chiasson Sonia,
Girard Denis
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0306209
Subject(s) - biology , socs3 , microbiology and biotechnology , cytokine , signal transduction , cycloheximide , p38 mitogen activated protein kinases , suppressor of cytokine signaling 1 , cytokine receptor , socs5 , mapk/erk pathway , immunology , stat3 , biochemistry , protein biosynthesis , gene , suppressor
Interleukin‐4 (IL‐4) is a CD132‐dependent cytokine known to activate the Jak‐STAT pathway in different cells and cell lines. Although IL‐4 has been demonstrated previously to be an agonist in human neutrophils, its capacity to activate different cell signaling pathways in these cells has never been investigated. Two types of IL‐4 receptor (IL‐4R) exist: the Type I (CD132/IL‐4R1 heterodimer) and the Type II (IL‐4Rα/IL‐13Rα1 heterodimer). In a previous study, we demonstrated that neutrophils express the Type I receptor. Herein, using flow cytometry, we demonstrated that neutrophils, unlike U‐937 cells, do not express IL‐13Rα1 and IL‐13Rα2 and confirmed the expression of CD132 and IL‐4Rα on their surface. We also demonstrated that IL‐4 induced phosphorylation of Syk, p38, Erk‐1/2, JNK, Jak‐1, Jak‐2, STAT6, and STAT1 and that treatment of cells with the inhibitors piceatannol, SB203580, PD98059, or AG490 reversed the ability of IL‐4 to delay neutrophil apoptosis. Using RT‐PCR, we demonstrated for the first time that neutrophils express mRNA for all suppressor of cytokine signaling (SOCS) members, namely SOCS1–7 and cytokine‐inducible Src homology 2 protein. It is interesting that IL‐4 increased expression of SOCS3 at the mRNA and protein levels. The effect of IL‐4 on SOCS3 protein expression was increased markedly when the proteasome inhibitor MG132 was added to the cultures, but this was inhibited by cycloheximide, suggesting that SOCS3 is de novo‐synthesized in response to IL‐4. We conclude that neutrophils express only the Type I IL‐4R on their surface and that IL‐4 signals via different cell signaling pathways, including the Jak/STAT/SOCS pathway.