An AP‐1 site in the promoter of the human IL‐5Rα gene is necessary for promoter activity in eosinophilic HL60 cells

Baltus, Belinda; Dijk, Thamar B. van; Caldenhoven, Eric; Zanders, Ed; Raaijmakers, J. A. M.; Lammers, Jan‐Willem J.; Koenderman, Leo; Groot, Rolf P. de

doi:10.1016/s0014-5793(98)00991-0

Cited by 12 publications

(7 citation statements)

References 29 publications

(43 reference statements)

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“…Although the IL-5 receptor has been documented to be expressed in dif-HC15 as determined by mRNA analyses and by ligand binding experiments, the surface expression of the receptors for IL-5 family members has not been reported (56–58). Because we are interested in the priming mechanisms involved with IL-5 family members, we evaluated the expression profile of the receptors for all three family members in the naïve and dif-HC15 cells in comparison to that in human primary blood eosinophils utilizing PE/FITC-conjugated antibodies targeting the specific α subunit of each IL-5 family receptor.…”

Section: Resultsmentioning

confidence: 99%

Chemoattractant-Induced Signaling via the Ras–ERK and PI3K–Akt Networks, along with Leukotriene C4 Release, Is Dependent on the Tyrosine Kinase Lyn in IL-5– and IL-3–Primed Human Blood Eosinophils

Zhu

Bertics

2011

The Journal of Immunology

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Human blood eosinophils exhibit a hyper-active phenotype in response to chemotactic factors following cell “priming” with IL-5 family cytokines. Earlier work has identified ERK1/2 as molecular markers for IL-5 priming, and herein we show that IL-3, a member of IL-5 family, also augments fMLP-stimulated ERK1/2 phosphorylation in primary eosinophils. Besides ERK1/2, we also observed an enhancement of chemotactic factor-induced Akt phosphorylation following IL-5 priming of human blood eosinophils. Administration of a peptide antagonist that targets the Src family member Lyn prior to cytokine (IL-5/IL-3) priming of blood eosinophils inhibited the synergistic increase of fMLP-induced activation of Ras, ERK1/2 and Akt, as well as the release of the proinflammatory factor leukotriene-C4. In the current study, we also examined a human eosinophil-like cell line HL-60 clone-15, and observed that these cells exhibited significant surface expression of IL-3 and GM-CSF receptors, as well as ERK1/2 phosphorylation in response to the addition of IL-5 family cytokines or the chemotactic factors fMLP, CCL5 and CCL11. Consistent with the surface profile of IL-5 family receptors, HL-60 clone-15 recapitulated the enhanced fMLP-induced ERK1/2 phosphorylation observed in primary blood eosinophils following priming with IL-3/GM-CSF, and siRNA-mediated knockdown of Lyn expression completely abolished the synergistic effects of IL-3 priming on fMLP-induced ERK1/2 phosphorylation. Altogether, our data reveal a central role for Lyn in the mechanisms of IL-5 family priming, and suggest that Lyn contributes to the up-regulation of the Ras-ERK1/2 and PI3K-Akt cascades as well as the increased leukotriene-C4 release observed in response to fMLP in “primed” eosinophils.

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Section: Resultsmentioning

confidence: 99%

Chemoattractant-Induced Signaling via the Ras–ERK and PI3K–Akt Networks, along with Leukotriene C4 Release, Is Dependent on the Tyrosine Kinase Lyn in IL-5– and IL-3–Primed Human Blood Eosinophils

Zhu

Bertics

2011

The Journal of Immunology

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“…For CaMKIV it has been suggested that it can phosphorylate CREB in vivo because it shows nuclear localization. 52 Although a role for CREB in myeloid cells has been proposed in mediating cytokine or chemokine effector functions, [53][54][55][56] it remains to be determined if CREB and CREM are physiologic substrates for CKLiK in human granulocytes. Indeed we were able to demonstrate CREB phosphorylation by IL-8 in human PMNs (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of CKLiK, a novel granulocyte Ca++/calmodulin-dependent kinase

Verploegen

Lammers

Koenderman

et al. 2000

Blood

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Human granulocytes are characterized by a variety of specific effector functions involved in host defense. Several widely expressed protein kinases have been implicated in the regulation of these effector functions. A polymerase chain reaction–based strategy was used to identify novel granulocyte-specific kinases. A novel protein kinase complementary DNA with an open reading frame of 357 amino acids was identified with homology to calcium-calmodulin–dependent kinase I (CaMKI). This has been termed CaMKI-like kinase (CKLiK). Analysis of CKLiK messenger RNA (mRNA) expression in hematopoietic cells demonstrated an almost exclusive expression in human polymorphonuclear leukocytes (PMN). Up-regulation of CKLiK mRNA occurs during neutrophilic differentiation of CD34+ stem cells. CKLiK kinase activity was dependent on Ca++ and calmodulin as analyzed by in vitro phosphorylation of cyclic adenosine monophosphate responsive element modulator (CREM). Furthermore, CKLiK- transfected cells treated with ionomycin demonstrated an induction of CRE- binding protein (CREB) transcriptional activity compared to control cells. Additionally, CaMK-kinaseα enhanced CKLiK activity. In vivo activation of CKLiK was shown by addition of interleukin (IL)-8 to a myeloid cell line stably expressing CKLiK. Furthermore inducible activation of CKLiK was sufficient to induce extracellular signal-related kinase (ERK) mitogen-activated protein (MAP) kinase activity. These data identify a novel Ca++/calmodulin-dependent PMN- specific kinase that may play a role in Ca++-mediated regulation of human granulocyte functions.

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“…Two days after transfection cells were harvested for CAT assays. CAT assays were performed as described previously [34]. CMV-LacZ co-transfection and ␤-galactosidase assays were used to correct for variations in transfection efficiency.…”

Section: Transient Transfection and Cat Assaymentioning

confidence: 99%

C/EBP regulates the promoter of the eosinophil-derived neurotoxin/RNS2 gene in human eosinophilic cells

Baltus¹,

Buitenhuis²,

Dijk³

et al. 1999

Journal of Leukocyte Biology

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An AP‐1 site in the promoter of the human IL‐5Rα gene is necessary for promoter activity in eosinophilic HL60 cells

Cited by 12 publications

References 29 publications

Chemoattractant-Induced Signaling via the Ras–ERK and PI3K–Akt Networks, along with Leukotriene C4 Release, Is Dependent on the Tyrosine Kinase Lyn in IL-5– and IL-3–Primed Human Blood Eosinophils

Chemoattractant-Induced Signaling via the Ras–ERK and PI3K–Akt Networks, along with Leukotriene C4 Release, Is Dependent on the Tyrosine Kinase Lyn in IL-5– and IL-3–Primed Human Blood Eosinophils

Identification and characterization of CKLiK, a novel granulocyte Ca++/calmodulin-dependent kinase

C/EBP regulates the promoter of the eosinophil-derived neurotoxin/RNS2 gene in human eosinophilic cells

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