Involvement of protein kinase Cδ in iron chelator-induced IL-8 production in human intestinal epithelial cells

Choi, Eun‐Young; Lee, SungGa; Oh, Hyun-Mee; Kim, Young-Dae; Choi, Eun‐Ju; Kim, Sang-Hyun; Kim, Sang–Wook; Choi, Suck-Chei; Jun, Chang‐Duk

doi:10.1016/j.lfs.2006.09.044

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…Immunoblot analysis demonstrated that TG treatment specifically increased PKC phosphorylation at Thr 538 within the activation loop, whereas phosphorylation observed at known activating sites in PKC␣/␤II (Thr 638/641 ), PKC␦ (Thr 505 ), or PKC␦ (Ser 643 ) (48,49,(51)(52)(53) was not significantly altered (Fig. 4A).…”

Section: Er Stress Induces Ca 2ϩ -Dependent Phosphorylation and Localmentioning

confidence: 98%

Protein Kinase Cθ Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum

Sakaki

Kaufman

2008

Journal of Biological Chemistry

168

140

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Autophagy is an evolutionally conserved process for the bulk degradation of cytoplasmic proteins and organelles. Recent observations indicate that autophagy is induced in response to cellular insults that result in the accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER). However, the signaling mechanisms that activate autophagy under these conditions are not understood. Here, we report that ER stress-induced autophagy requires the activation of protein kinase C (PKC), a member of the noveltype PKC family. Induction of ER stress by treatment with either thapsigargin or tunicamycin activated autophagy in immortalized hepatocytes as monitored by the conversion LC3-I to LC3-II, clustering of LC3 into dot-like cytoplasmic structures, and electron microscopic detection of autophagosomes. Pharmacological inhibition of PKC or small interfering RNA-mediated knockdown of PKC prevented the autophagic response to ER stress. Treatment with ER stressors induced PKC phosphorylation within the activation loop and localization of phospho-PKC to LC3-containing dot structures in the cytoplasm. However, signaling through the known unfolded protein response sensors was not required for PKC activation. PKC activation and stress-induced autophagy were blocked by chelation of intracellular Ca 2؉ with BAPTA-AM. PKC was not activated or required for autophagy in response to amino acid starvation. These observations indicate that Ca 2؉ -dependent PKC activation is specifically required for autophagy in response to ER stress but not in response to amino acid starvation.

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Section: Er Stress Induces Ca 2ϩ -Dependent Phosphorylation and Localmentioning

confidence: 98%

Protein Kinase Cθ Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum

Sakaki

Kaufman

2008

Journal of Biological Chemistry

168

140

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“…Indeed, a large-scale transcriptome analysis of DFO-treated intestinal epithelial cells indicated that several genes involved in inflammatory signaling were activated at the transcriptional level (Choi et al, 2004). Incubation of human intestinal epithelial HT-29 cells with DFO increased the expression of INTERLEUKIN-8 (IL-8) mRNA as well as the release of IL-8 protein (Choi et al, 2004(Choi et al, , 2007a(Choi et al, , 2007b. The CHEMOKINE (C-C MOTIF) LIGAND20 (CCL20) involved in the proinflammatory responses as well as the adaptive response accumulates in epithelial intestinal cells in response to DFO, indicating that siderophore can also trigger adaptive immune responses (Lee et al, 2005).…”

Section: Siderophores Trigger An Immunity Programmentioning

confidence: 99%

“…In these reports, the activation of immune responses is reversed by the use of ferri-siderophore, indicating that the immune-stimulating effect of DFO is related to its iron-chelating capacity. The accumulation of IL-8 in HT-29 epithelial intestinal cells through DFO requires the activity of the protein kinase C and the mitogen-activated protein kinase EXTRACELLULAR SIGNAL REGULATED KINASE1/2 and p38 (Choi et al, 2007a(Choi et al, , 2007b. Thus, DFO can display an immunostimulating activity in animal cells through activation of phosphorylation cascades.…”

Section: Siderophores Trigger An Immunity Programmentioning

confidence: 99%

Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores

et al. 2014

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Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H 2 O 2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity.

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“…Five micrograms of total RNAs isolated from cells were treated with RNase-free DNase (BD Pharmingen) and then used to generate first-strand cDNAs using a RevertAid first-strand cDNA synthesis kit with 500 ng of oligo(dT) [12][13][14][15][16][17][18] primers. PCR primers were designed with ABI PRISM Primer Express 2.0 (Applied Biosystems) and made by Geno Tech Corp (Korea).…”

Section: Rt-pcrmentioning

confidence: 99%

A Novel Pathway Responsible for Lipopolysaccharide-Induced Translational Regulation of TNF-α and IL-6 Expression Involves Protein Kinase C and Fascin

Kim

Lee

Suk

et al. 2011

The Journal of Immunology

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Fascin, as a substrate of protein kinase C (PKC), is a well-known cytoskeletal regulatory protein required for cell migration, invasion, and adhesion in normal and cancer cells. In an effort to identify the role of fascin in PKC-mediated cellular signaling, its expression was suppressed by stable transfection of specific short hairpin RNAs (shRNAs) in mouse monocytic leukemia RAW264.7 cells. Suppression of fascin expression resulted in impaired cellular migration and invasion through extracellular matrix proteins. Unexpectedly, the specific shRNA transfectants exhibited a marked reduction in LPS-induced expression of TNF-α and IL-6 by blocking the translation of their mRNAs. Transient transfection assay using a luciferase expression construct containing the 3′ untranslated region of TNF-α or IL-6 mRNA revealed a significant reduction in both LPS- and PMA- (the direct activator of PKC) induced reporter activity in cells transfected with fascin-specific shRNA, indicating that fascin-mediated translational regulation targeted 3′ untranslated region. Furthermore, LPS-induced translational activation of reporter expression was blocked by a pharmacological inhibitor of PKC, and the dominant-negative form of PKCα attenuated LPS-induced translational activation. The same type of regulation was also observed in the human monocytic leukemia cell line THP-1 and in mouse peritoneal macrophages. These data demonstrate the involvement of fascin in the PKC-mediated translational regulation of TNF-α and IL-6 expression during the LPS response.

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Involvement of protein kinase Cδ in iron chelator-induced IL-8 production in human intestinal epithelial cells

Cited by 11 publications

References 45 publications

Protein Kinase Cθ Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum

Protein Kinase Cθ Is Required for Autophagy in Response to Stress in the Endoplasmic Reticulum

Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores

A Novel Pathway Responsible for Lipopolysaccharide-Induced Translational Regulation of TNF-α and IL-6 Expression Involves Protein Kinase C and Fascin

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