NGF rescues human B lymphocytes from anti-IgM induced apoptosis by activation of PKCζ

Kronfeld, Ilana; Kazimirsky, Gila; Gelfand, Erwin W.; Brodie, Chaya

doi:10.1002/1521-4141(200201)32:1<136::aid-immu136>3.0.co;2-t

Cited by 40 publications

(26 citation statements)

References 61 publications

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“…Nuclear translocation of PKCz has also been observed in other cell type that coincides with the inhibition of apoptosis. 25 Therefore, it is our hypothesis that PKCz may function as an antiapoptotic signal by interrupting nuclear signaling such as NF-kB activation, p53 accumulation, and Bax expression.…”

Section: Discussionmentioning

confidence: 99%

p38 kinase mediates nitric oxide-induced apoptosis of chondrocytes through the inhibition of protein kinase C ζ by blocking autophosphorylation

et al. 2005

Cell Death Differ

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This study investigated the molecular mechanisms underlying inhibition of protein kinase C (PKC) f by p38 kinase during nitric oxide (NO)-induced apoptosis of chondrocytes. Coimmunoprecipitation experiments showed that activation of p38 kinase following addition of an NO donor resulted in a physical association between PKCf and p38 kinase. Direct interaction of p38 kinase with PKCf was confirmed in vitro using p38 kinase and PKCf recombinant proteins. p38 kinase interacts with the regulatory domain of PKCf and its association blocked PKCf autophosphorylation. Micro LC-MS/MS analysis using recombinant proteins indicated that the interaction of p38 kinase with PKCf blocked autophosphorylation of PKCf on Thr-560, which is required for PKCf activation. Collectively, our results demonstrate a novel mechanism of PKCf regulation: following activation by the production of NO, p38 kinase binds directly to the PKCf regulatory domain, preventing PKCf autophosphorylation on Thr-560, thereby inhibiting PKCf activation.

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Section: Discussionmentioning

confidence: 99%

p38 kinase mediates nitric oxide-induced apoptosis of chondrocytes through the inhibition of protein kinase C ζ by blocking autophosphorylation

et al. 2005

Cell Death Differ

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“…It has been demonstrated that PKC, Ras-ERK and PI3K pathways are involved in the survival of B lymphocytes [29][30][31]. Among these signaling pathways, PI3K and Ras signaling pathways are activated by CD40 stimulation [9,11].…”

Section: Discussionmentioning

confidence: 99%

Kinetics and signaling requirements of CD40‐mediated protection from B cell receptor‐induced apoptosis

et al. 2003

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In the present study we used a human follicular lymphoma cell line, HF1A3, as an in vitro model for the antigen-driven selection process in germinal centers. Apoptosis can be induced in HF1A3 cells by B cell receptor (BCR) stimulation, but the molecular mechanisms and kinetics of this process are largely unknown. We demonstrate here that there is over 12 h delay between receptor activation and the execution phase of apoptosis, i.e. disruption of mitochondrial membrane potential, release of cytochrome c from mitochondria, caspase-3 activation and DNA fragmentation. New protein synthesis is required for mitochondrial alterations and subsequent apoptosis to occur, as these processes are completely blocked by the protein synthesis inhibitor cycloheximide. All the apoptotic events induced by BCR triggering are completely reversed by CD40 ligation with anti-CD40 antibody. CD40 ligation can reverse the apoptotic process in HF1A3 cells almost until the first mitochondrial events take place demonstrating that CD40-mediated protection operates very fast and at or before mitochondrial phase of apoptosis. Using specific inhibitors of cell signaling we could demonstrate that Raf-extracellular signal-regulated kinase, phosphatidylinositol 3-kinase, p38 or protein kinase C activation pathways are not involved in CD40-mediated protection from BCR-induced apoptosis in HF1A3 cells.

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“…As demonstrated in studies performed on neuronal cells, binding of NGF to TrkA activates Ras, PI3K, phospholipase Cg1, and downstream signaling pathways, including MAPKs (9). Very little information is available on the signaling pathways elicited by TrkA activation in immune cells (10)(11)(12).…”

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confidence: 99%

Nerve Growth Factor Downregulates Inflammatory Response in Human Monocytes through TrkA

Prencipe

Minnone

Strippoli

et al. 2014

The Journal of Immunology

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Nerve growth factor (NGF) levels are highly increased in inflamed tissues, but their role is unclear. We show that NGF is part of a regulatory loop in monocytes: inflammatory stimuli, while activating a proinflammatory response through TLRs, upregulate the expression of the NGF receptor TrkA. In turn, NGF, by binding to TrkA, interferes with TLR responses. In TLR-activated monocytes, NGF reduces inflammatory cytokine production (IL-1β, TNF-α, IL-6, and IL-8) while inducing the release of anti-inflammatory mediators (IL-10 and IL-1 receptor antagonist). NGF binding to TrkA affects TLR signaling, favoring pathways that mediate inhibition of inflammatory responses: it increases Akt phosphorylation, inhibits glycogen synthase kinase 3 activity, reduces IκB phosphorylation and p65 NF-κB translocation, and increases nuclear p50 NF-κB binding activity. Use of TrkA inhibitors in TLR-activated monocytes abolishes the effects of NGF on the activation of anti-inflammatory signaling pathways, thus increasing NF-κB pathway activation and inflammatory cytokine production while reducing IL-10 production. PBMC and mononuclear cells obtained from the synovial fluid of patients with juvenile idiopathic arthritis show marked downregulation of TrkA expression. In ex vivo experiments, the addition of NGF to LPS-activated juvenile idiopathic arthritis to both mononuclear cells from synovial fluid and PBMC fails to reduce the production of IL-6 that, in contrast, is observed in healthy donors. This suggests that defective TrkA expression may facilitate proinflammatory mechanisms, contributing to chronic tissue inflammation and damage. In conclusion, this study identifies a novel regulatory mechanism of inflammatory responses through NGF and its receptor TrkA, for which abnormality may have pathogenic implications for chronic inflammatory diseases

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NGF rescues human B lymphocytes from anti-IgM induced apoptosis by activation of PKCζ

Cited by 40 publications

References 61 publications

p38 kinase mediates nitric oxide-induced apoptosis of chondrocytes through the inhibition of protein kinase C ζ by blocking autophosphorylation

p38 kinase mediates nitric oxide-induced apoptosis of chondrocytes through the inhibition of protein kinase C ζ by blocking autophosphorylation

Kinetics and signaling requirements of CD40‐mediated protection from B cell receptor‐induced apoptosis

Nerve Growth Factor Downregulates Inflammatory Response in Human Monocytes through TrkA

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