Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

Amcheslavsky, Alla; Zou, Wei; Bar‐Shavit, Zvi

doi:10.1074/jbc.m409138200

Cited by 22 publications

(23 citation statements)

References 68 publications

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“…The discrepancy was not due to differences in cell density or duration of culture since we observed an even more reduced osteoclastogenic ability of 4-1BB -/-BMM in culture using their method than ours (Supporting Information 4). BALB/c and C57BL/6 strains have different immunologic characteristics and a difference in osteoclastogenesis of BMM from these two strains has been previously reported [24]. Whether the difference in genetic background caused the discrepancy warrants further investigation.…”

Section: Discussionmentioning

confidence: 86%

The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling

et al. 2008

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The 4-1BB is a costimulatory molecule similar to the receptor activator of NF-jB ligand (RANKL), both of which are key factors for the differentiation of osteoclasts and are expressed mainly by activated T cells. The 4-1BB shares common signaling pathways with RANK, suggesting a potential role in osteoclastogenesis. In this study, the role of 4-1BB and 4-1BB ligand (4-1BBL) in osteoclastogenesis was investigated using 4-1BB -/-and 4-1BB +/+ mice. Osteoclast precursors normally express 4-1BB and 4-1BBL after exposure to RANKL, which was confirmed by semi-quantitative RT-PCR and flow cytometry. The 4-1BB -/-mice had a slightly increased bone mass accompanied by a reduced osteoclastogenic ability of 4-1BB -/-bone marrow-derived macrophages (BMM) ex vivo. In addition, 4-1BB -/-BMM demonstrated hypophosphorylation of JNK and p38 and decreased induction of c-Fos in response to RANKL stimulation. Retroviral transduction of wild-type as well as partiallength 4-1BB, which lacks TNF receptor-associated factor 2-binding sites for signaling, restored the osteoclastogenic ability of 4-1BB -/-BMM. Furthermore, both recombinant 4-1BB and 4-1BBL enhanced RANKL-induced osteoclastogenesis by 4-1BB +/+ BMM and the induction of c-Fos and NFATc1.Together, these results indicate that 4-1BBL and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling, findings that may delineate the complex nature of the 4-1BBL and 4-1BB interaction.

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Section: Discussionmentioning

confidence: 86%

The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling

et al. 2008

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“…We have tried to determine secretion of TNF-α in response to rutin with no success. The release of TNF-α from C57BL/6-derived BMM was low due to lower translation, comparing with that from BALB/c-derived one (Amcheslavsky et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-α by inhibiting activation of NF-κB

et al. 2008

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“…Indeed, we find no evidence that internalization of CD154 once it becomes expressed on the surface of T cells and binds CD40 explains impaired CD154 induction in CD4 ϩ T cells from HIV-1 ϩ patients. Additional levels of control of CD154 are likely to exist because regulation of CD154 is similar to that of TNF-␣ and expression of this cytokine can be controlled at the level of translation (36).…”

Section: Discussionmentioning

confidence: 99%

Role of CD40-Dependent Down-Regulation of CD154 in Impaired Induction of CD154 in CD4+ T Cells from HIV-1-Infected Patients

Subauste

Wessendarp

2007

The Journal of Immunology

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CD40-CD154 interaction is pivotal for cell-mediated immunity. There are contradictory reports on whether HIV-1 infection impairs CD154 induction. The interaction between CD40 and CD154 is important not only because it results in activation of APCs but also because it controls CD154 by diminishing expression of this molecule. Compared with healthy controls, CD4+ T cells from HIV-1+ patients had impaired induction of CD154 when T cell activation was mediated by CD40+ APCs. In contrast, T cell activation in the absence of these cells resulted in normal CD154 expression. CD154 induction in HIV-1+ patients and controls were similar upon blockade of CD40-CD154 binding. Defective regulation of CD154 appeared to occur downstream of the control of mRNA levels because up-regulation of CD154 mRNA was not impaired by HIV-1 infection. This work identifies CD40 as a mediator of impaired CD154 induction in HIV-1 infection and explains why this defect was not detected by studies where T cell activation was triggered independently of CD40+ APCs. In addition, dysregulation of CD154 in HIV-1 infection likely contributes to immunodeficiency because diminished expression of CD154 induced by CD40 is of functional relevance, resulting in decreased dendritic cell maturation.

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Toll-like Receptor 9 Regulates Tumor Necrosis Factor-α Expression by Different Mechanisms

Cited by 22 publications

References 68 publications

The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling

The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling

Rutin inhibits osteoclast formation by decreasing reactive oxygen species and TNF-α by inhibiting activation of NF-κB

Role of CD40-Dependent Down-Regulation of CD154 in Impaired Induction of CD154 in CD4+ T Cells from HIV-1-Infected Patients

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