SOCS3 expression induced by PIM2 requires PKC and PI3K signaling

Narayana, Y.; Bansal, Kushagra; Sinha, Akhauri Yash; Kapoor, Nisha; Puzo, Germain; Gilleron, Martine; Balaji, Kithiganahalli Narayanaswamy

doi:10.1016/j.molimm.2009.06.019

Cited by 21 publications

(20 citation statements)

References 44 publications

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“…Significantly, PKCs are important kinases that often effectuate the effects of the PI3K pathway across diverse cell types (43,50,51). Thus, we examined the role for PKC in the contribution to the ability of TLR2 and NOD receptors in suppressing the inhibitory effects of CTLA-4 and TGF-␤ on DC maturation.…”

Section: Integration Of Pkc-mapk-nf-b Signaling Pathways During Tlr2 mentioning

confidence: 99%

Cooperative Regulation of NOTCH1 Protein-Phosphatidylinositol 3-Kinase (PI3K) Signaling by NOD1, NOD2, and TLR2 Receptors Renders Enhanced Refractoriness to Transforming Growth Factor-β (TGF-β)- or Cytotoxic T-lymphocyte Antigen 4 (CTLA-4)-mediated Impairment of Human Dendritic Cell Maturation

Ghorpade

Kaveri

Bayry

et al. 2011

Journal of Biological Chemistry

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Dendritic cells (DCs) as sentinels of the immune system are important for eliciting both primary and secondary immune responses to a plethora of microbial pathogens. Cooperative stimulation of a complex set of pattern-recognition receptors, including TLR2 and nucleotide-binding oligomerization domain (NOD)-like receptors on DCs, acts as a rate-limiting factor in determining the initiation and mounting of the robust immune response. It underscores the need for "decoding" these multiple receptor interactions. In this study, we demonstrate that TLR2 and NOD receptors cooperatively regulate functional maturation of human DCs. Intriguingly, synergistic stimulation of TLR2 and NOD receptors renders enhanced refractoriness to TGF-␤-or CTLA-4-mediated impairment of human DC maturation. Signaling perturbation data suggest that NOTCH1-PI3K signaling dynamics assume critical importance in TLR2-and NOD receptor-mediated surmounting of CTLA-4-and TGF-␤-suppressed maturation of human DCs. Interestingly, the NOTCH1-PI3K signaling axis holds the capacity to regulate DC functions by virtue of PKC␦-MAPK-dependent activation of NF-B. This study provides mechanistic and functional insights into TLR2-and NOD receptor-mediated regulation of DC functions and unravels NOTCH1-PI3K as a signaling cohort for TLR2 and NOD receptors. These findings serve in building a conceptual foundation for the design of improved strategies for adjuvants and immunotherapies against infectious diseases.

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Section: Integration Of Pkc-mapk-nf-b Signaling Pathways During Tlr2 mentioning

confidence: 99%

Cooperative Regulation of NOTCH1 Protein-Phosphatidylinositol 3-Kinase (PI3K) Signaling by NOD1, NOD2, and TLR2 Receptors Renders Enhanced Refractoriness to Transforming Growth Factor-β (TGF-β)- or Cytotoxic T-lymphocyte Antigen 4 (CTLA-4)-mediated Impairment of Human Dendritic Cell Maturation

Ghorpade

Kaveri

Bayry

et al. 2011

Journal of Biological Chemistry

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“…We hypothesized that fenretinide had an by guest, on May 11, 2018 www.jlr.org Downloaded from the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB) (also called Akt) pathway ( 28,29 ), the PI3K-PKC pathway ( 30,31 ), and the mitogen-activated protein kinase (MAPK) signaling pathways ( 32,33 ). The MAPKs consist of three major families, including extracellular-signal-regulated kinase (ERK), cJNK, and p38.…”

Section: Fenretinide Inhibited Il-1 ␤ Il-6 and Pge2 Cytokine Exprementioning

confidence: 99%

“…The MAPKs consist of three major families, including extracellular-signal-regulated kinase (ERK), cJNK, and p38. Activation of PI3K-Akt and PI3K-PKC also infl uences the phosphorylation of inhibitor of nuclear factor kappa-B kinase subunit alpha (IkB), nuclear factor kappaB (NF-kB) ( 30,34 ) and MAPK activities ( 35,36 ). To determine which immune signaling pathways are infl uenced by fenretinide, Raw 264.7 cells were treated with fenretinide (5 M) or control vehicle ethanol for 4 h. Then the cells were unstimulated or stimulated with A .…”

Section: Fenretinide Inhibited Il-1 ␤ Il-6 and Pge2 Cytokine Exprementioning

confidence: 99%

Fenretinide inhibited de novo ceramide synthesis and proinflammatory cytokines induced by Aggregatibacter actinomycetemcomitans

Valerio

Bielawski

2013

Journal of Lipid Research

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Sphingolipids play important roles in regulating cell growth, death, senescence, adhesion, migration, infl ammation, angiogenesis, and intracellular traffi cking. Among the sphingolipids, ceramides have been recognized as "second messengers" in modulating immune signaling transduction ( 1 ). Ceramides can be generated via three pathways ( 2 ) ( Fig. 1 ). The fi rst pathway is a de novo pathway, which occurs in the endoplasmic reticulum (ER) and possibly at ER-associated membranes, such as the perinuclear membrane and mitochondria-associated membranes. De novo synthesis of ceramides begins with the condensation of palmitate and serine to form 3-keto-dihydrosphingosine by serine-palmitoyl transferase (SPT). 3-Keto-dihydrosphingosine is reduced to dihydrosphingosine (dhSph) and followed by acylation to produce dihydroceramide (dhCer). Finally, dhCer is catalyzed by dihydroceramide desaturase (DEGS) to generate ceramides. The second pathway is the sphingomyelinase (SMase) pathway, which occurs in the plasma membrane and the endosomal/lysosomal compartments. Ceramides are generated by hydrolysis of sphingomyelin (SM) by SMase. The third pathway is the salvage pathway, which occurs in the acidic subcellular compartments, such as the late endosomes and the lysosomes. In the acidic subcellular compartments, complex sphingolipids and glycosphingolipids are degraded to form sphingosine (Sph). Sph can be converted to ceramides by ceramide synthase. Conversely, ceramides can Abstract Ceramides play an essential role in modulating immune signaling pathways and proinfl ammatory cytokine production in response to infectious pathogens, stress stimuli, or chemotherapeutic drugs. In this study, we demonstrated that Aggregatibacter actinomycetemcomitans , the path ogen for aggressive periodontitis, induced de novo synthesis of ceramide in Raw 264.7 cells. In addition, we identifi ed that fenretinide, a synthetic retinoid, suppressed the de novo synthesis of ceramide induced by A. actinomycetemcomitans. Moreover, fenretinide attenuated interleukin (IL)-1 ␤ , IL-6, and cyclooxygenase-2 mRNA expression induced by A. actinomycetemcomitans. Fenretinide also decreased IL-1 ␤ , IL-6, and prostaglandin E2 proinfl ammatory cytokine levels in Raw 264.7 cells induced by A. actinomycetemcomitans. However, fenretinide had no signifi cant effects on tumor necrosis factor alpha mRNA or protein levels. Furthermore, we showed that fenretinide inhibited the janus kinase-signal transducer and activator of transcription, phosphatidylinositol 3-kinase-Akt, protein kinase C, and nuclear factor-kappaB signaling pathways, whereas fenretinide up-regulated the mitogen-activated protein kinase signaling pathways after bacterial stimulation. This study emphasizes the de novo ceramide synthesis pathway in response to bacterial stimulation and demonstrates the anti-infl ammatory role of fenretinide in the bacteria-induced immune response.

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“…In this context, integration of key signaling centers modulating immunity to pathogenic mycobacterial infections remains unexplored. However, macrophages as sentinels are known to tailor differential immune responses to infections with pathogenic mycobacteria, including Mycobacterium tuberculosis, Mycobacterium bovis, etc., by utilizing dynamic interplay of signaling networks (14)(15)(16)(17)(18)(19). We propose SHH signaling to constitute one such signaling network.…”

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confidence: 99%

Sonic hedgehog-Dependent Induction of MicroRNA 31 and MicroRNA 150 Regulates Mycobacterium bovis BCG-Driven Toll-Like Receptor 2 Signaling

Ghorpade

Holla

Kaveri

et al. 2013

Molecular and Cellular Biology

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SOCS3 expression induced by PIM2 requires PKC and PI3K signaling

Cited by 21 publications

References 44 publications

Cooperative Regulation of NOTCH1 Protein-Phosphatidylinositol 3-Kinase (PI3K) Signaling by NOD1, NOD2, and TLR2 Receptors Renders Enhanced Refractoriness to Transforming Growth Factor-β (TGF-β)- or Cytotoxic T-lymphocyte Antigen 4 (CTLA-4)-mediated Impairment of Human Dendritic Cell Maturation

Cooperative Regulation of NOTCH1 Protein-Phosphatidylinositol 3-Kinase (PI3K) Signaling by NOD1, NOD2, and TLR2 Receptors Renders Enhanced Refractoriness to Transforming Growth Factor-β (TGF-β)- or Cytotoxic T-lymphocyte Antigen 4 (CTLA-4)-mediated Impairment of Human Dendritic Cell Maturation

Fenretinide inhibited de novo ceramide synthesis and proinflammatory cytokines induced by Aggregatibacter actinomycetemcomitans

Sonic hedgehog-Dependent Induction of MicroRNA 31 and MicroRNA 150 Regulates Mycobacterium bovis BCG-Driven Toll-Like Receptor 2 Signaling

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