Lipopolysaccharide-induced c-Jun NH2-terminal Kinase Activation in Human Neutrophils

Arndt, Patrick; Suzuki, Naoki; Avdi, Natalie J.; Malcolm, Kenneth C.; Worthen, G. Scott

doi:10.1074/jbc.m309901200

Cited by 140 publications

(152 citation statements)

References 76 publications

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“…101 In neutrophils, LPS-induced JNK activation involves the participation of the protein tyrosine kinase, Syk, and PI3K. 102 Taken together, these findings suggest that the receptor complex may include many more proteins than that shown in Figures 1 and 2.…”

Section: Mitogen-activated Protein Kinasesmentioning

confidence: 60%

Lipopolysaccharide signaling in endothelial cells

Dauphinee

Karsan

2006

Laboratory Investigation

529

433

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Sepsis is the systemic immune response to severe bacterial infection. The innate immune recognition of bacterial and viral products is mediated by a family of transmembrane receptors known as Toll-like receptors (TLRs). In endothelial cells, exposure to lipopolysaccharide (LPS), a major cell wall constituent of Gramnegative bacteria, results in endothelial activation through a receptor complex consisting of TLR4, CD14 and MD2. Recruitment of the adaptor protein myeloid differentiation factor (MyD88) initiates an MyD88-dependent pathway that culminates in the early activation of nuclear factor-jB (NF-jB) and the mitogen-activated protein kinases. In parallel, a MyD88-independent pathway results in a late-phase activation of NF-jB. The outcome is the production of various proinflammatory mediators and ultimately cellular injury, leading to the various vascular sequelae of sepsis. This review will focus on the signaling pathways initiated by LPS binding to the TLR4 receptor in endothelial cells and the coordinated regulation of this pathway.

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Section: Mitogen-activated Protein Kinasesmentioning

confidence: 60%

Lipopolysaccharide signaling in endothelial cells

Dauphinee

Karsan

2006

Laboratory Investigation

529

433

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“…Moreover, for the first time we demonstrate that the constitutively activated Syk is required for B lymphoma growth. Syk induces multiple signaling pathways including PI3K, NF-B, phospholipase C-␥, and JNK (20,57,58). Curcumin has been shown to target NF-B, Akt, JNK, JAK, STAT3, and Src kinases in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth

Gururajan

Dasu

Shahidain

et al. 2007

The Journal of Immunology

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Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-xL, a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

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“…One of the signaling pathways activated by both TRIF and MyD88 involves the MAPK family of signaling kinases (11). Growing evidence indicates that different MAPKs play different roles in mediating expression of MyD88-associated versus TRIF-associated genes at either transcriptional levels via activation of transcription factors or at post-transcriptional levels via mRNA transcript stabilization (13)(14)(15)(16)(17)(18)(19). We and others (1, 3, 20 -22) noted previously that MPLA increased levels of not only TRIF-associated transcripts, such as IFIT1 (interferon-induced protein with tetratricopeptide repeats) and IFIT2, but also significant levels of NF-B-associated IL-10, TNF␣, IL-12, and co-stimulatory molecules, despite comparatively weak NF-B activation.…”

mentioning

confidence: 99%

Selective Activation of the p38 MAPK Pathway by Synthetic Monophosphoryl Lipid A

Cekic

Casella

Eaves

et al. 2009

Journal of Biological Chemistry

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TLR4 stimulation by lipopolysaccharide can cause both MAL/MyD88-and TRAM/TRIF (Toll IL-1 receptor domaincontaining adaptor-inducing IFN␤)-dependent signaling events. Monophosphoryl lipid A (MPLA), a low toxicity derivative of endotoxic lipopolysaccharide, enhances antibody responses, T cell expansion, and recall responses against antigens without causing excessive inflammatory side effects. Previously, we proposed that TRIF-biased activation of TLR4 by MPLA is responsible for its reduced toxicity while retaining potent adjuvant effects. However, some TRIF-associated genes, such as MCP-1, are only weakly expressed, and some MyD88-associated inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor ␣ and interleukin-10, are strongly activated after MPLA stimulation despite weak NF-B but strong IRF3 activation. We now report that synthetic derivatives of MPLA retained TRIF bias as compared with synthetic diphosphoryl lipid A, indicating a change in a single phosphoryl group is sufficient for TRIF-biased TLR4 stimulation. We extend our previous observations by showing that sMLA induces strong p38 MAPK but weak JNK activation, resulting in high IP-10 (interferon-inducible protein 10), tumor necrosis factor ␣, and interleukin-10 but low MCP-1 transcript levels. Results of this study identify a novel biochemical mechanism for regulation of sMLA-induced gene expression.

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Lipopolysaccharide-induced c-Jun NH2-terminal Kinase Activation in Human Neutrophils

Cited by 140 publications

References 76 publications

Lipopolysaccharide signaling in endothelial cells

Lipopolysaccharide signaling in endothelial cells

Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth

Selective Activation of the p38 MAPK Pathway by Synthetic Monophosphoryl Lipid A

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