Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-κB activity in LPS-stimulated mouse peritoneal macrophages and RAW 264.7 cells

Kim, Young‐Hee; Moon, Ji Sun; Lee, Kyoung Soon; Park, Sun Young; Cheong, JaeHun; Kang, Ho Sung; Lee, Hak Young; Kim, Han Do

doi:10.1016/j.bbrc.2003.12.153

Cited by 79 publications

(57 citation statements)

References 39 publications

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“…We showed that calcium/CaM is essential for TLR4 to activate many of its target genes, which is consistent with the fact that TMB-8, which prevents calcium release from intracellular stores, compromises LPS-induced tumoricidal activity of macrophages (27,28). Paradoxically, LPS cannot induce any increase in intracellular calcium concentrations (27)(28)(29)(30), or at best induces very weak calcium signals (31,32). However, it has been consistently reported that basal calcium concentrations in macrophages (100-200 nM) are higher than T cells (33)(34)(35), which is minimally sufficient for activating the CaM-Calcineurin pathway, leading to NFATc nuclear translocation and repression of basal-level NFkb activation in resting macrophages (33,36).…”

Section: Discussionmentioning

confidence: 99%

Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling

Lai

Wan

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Upon toll-like receptor 4 (TLR4) signaling in macrophages, the mammalian Swi/Snf-like BAF chromatin remodeling complex is recruited to many TLR4 target genes where it remodels their chromatin to promote transcription. Here, we show that, surprisingly, recruitment is not sufficient for chromatin remodeling; a second event, dependent on calcium/calmodulin (CaM), is additionally required. Calcium/CaM directly binds the HMG domain of the BAF57 subunit within the BAF complex. Calcium/CaM antagonists, including a CaM-binding peptide derived from BAF57, abolish BAF-dependent remodeling and gene expression without compromising BAF recruitment. BAF57 RNAi and BAF57 dominant negative mutants defective in CaM binding similarly impair the induction of BAF target genes. Our data implicate calcium/CaM in TLR4 signaling, and reveal a previously undescribed, recruitment-independent mode of regulation of the BAF complex that is probably achieved through a direct CaM-BAF interaction.

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Section: Discussionmentioning

confidence: 99%

Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling

Lai

Wan

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…A rise in intracellular Ca 2ϩ accompanies LPS stimulation of peritoneal macrophages and RAW 264.7 cells (Kim et al, 2004) and is crucial for the stimulation of TNF-␣ release in murine peritoneal macrophage (Chen et al, 2001). These investigators showed that the addition of LPS with thapsigargin, an inhibitor of the Ca 2ϩ -ATPase pump in the endoplasmic reticulum, produced a more efficient transcription of TNF-␣ mRNA, whereas chelation of intracellular Ca 2ϩ abolished the Ca 2ϩ -dependent TNF-␣ production.…”

Section: Discussionmentioning

confidence: 99%

Activation of the Adenosine A₃Receptor in RAW 264.7 Cells Inhibits Lipopolysaccharide-Stimulated Tumor Necrosis Factor-α Release by Reducing Calcium-Dependent Activation of Nuclear Factor-κB and Extracellular Signal-Regulated Kinase 1/2

Martin¹,

Pingle²,

Hallam³

et al. 2005

J Pharmacol Exp Ther

105

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Bacterial lipopolysaccharide (LPS) activates the immune system and promotes inflammation via Toll-like receptor (TLR) 4, which regulates the synthesis and release of tumor necrosis factor (TNF)-␣ and other inflammatory cytokines. Previous studies have shown that the nucleoside adenosine suppresses LPS-stimulated TNF-␣ release in human UB939 macrophages by activating an adenosine A 3 receptor (A 3 AR) subtype on these cells. In this study, we examined the mechanism(s) underlying A 3 AR-dependent inhibition of TNF-␣ release in a mouse (RAW 264.7) cell line. Treatment of RAW 264.7 cells with LPS (3 g/ml) increased TNF-␣ release, which was reduced in a dose-dependent manner by adenosine analogs N 6 -(3-iodobenzyl)-adenosine-5Ј-N-methyluronamide (IB-MECA) and R-phenylisopropyladenosine and reversed by selective A 3 AR blockade. The increase in TNF-␣ release was preceded by an increase in intracellular Ca 2ϩ levels. Inhibition of intracellular Ca 2ϩ release by IB-MECA, a selective agonist of the A 3 AR, or with BAPTA-AM, an intracellular Ca 2ϩ chelator, reduced LPSstimulated TNF-␣ release. Activation of the A 3 AR or inhibition of intracellular Ca 2ϩ release also reduced LPS-stimulated nuclear factor-B (NF-B) activation and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Similar inhibition by A 3 AR was observed for LPS-stimulated inducible nitric-oxide synthase. These data support the contention that inhibition of LPS-stimulated release of inflammatory molecules, such as TNF-␣ and NO via the A 3 AR, involves suppression of intracellular Ca 2ϩ signaling, leading to suppression of NF-B and ERK1/2 pathways.

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“…Kim et al reported that IκB kinase (IKK) activity in response to LPS was markedly inhibited by Ba 2+ modulators, including nifedipine. 33 Petranka et al also demonstrated that a cell-permeable Ca 2+ chelator, the acetoxymethyl ester of 1,2-bis (O-aminophenoxy) ethane-N,N, N',N'-tetraacetic acid (BAPTA/AM), reduced cytosolic Ca 2+ concomitant with a reduction in NF-κB binding activity and a reduction in IKK activity. 34 These observations suggest that calcium antagonists act in a signal transduction pathway upstream of IKK to mediate IκB phosphorylation.…”

Section: Nifedipine Cytokine Production and Stimulationmentioning

confidence: 99%

Calcium Channel Blockers Differentially Modulate Cytokine Production by Peripheral Blood Mononuclear Cells

Matsumori

Nishio

Nose

2010

Circ J

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Background: Calcium channel blockers (CCB) are known to modulate immune reactions, so the present study was performed to examine the effects of various CCBs that have shown different effects on transcription factors and on the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMC). Methods and Results:PBMC from healthy volunteers were isolated by Ficoll-paque density centrifugation. To study the effect of CCBs, the PBMC were stimulated with lipopolysaccharide or concanavalin A. After 24 h of incubation, the supernatants were harvested and the interleukin (IL)-1α, -1β, and -6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ levels were determined by specific enzyme-linked immunosorbent assay. The production of IL-1α and -1β stimulated with lipopolysaccharide was significantly increased in the presence of amlodipine. In contrast, nifedipine and verapamil suppressed the production of IL-1β, TNF-α, and IFN-γ. Amlodipine and diltiazem significantly increased production of IL-1α stimulated with concanavalin A. Nifedipine inhibited production of IL-1α, IL-6, and IFN-γ. Verapamil suppressed production of IFN-γ.Conclusions: Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent. (Circ J 2010; 74: 567 - 571)

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Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-κB activity in LPS-stimulated mouse peritoneal macrophages and RAW 264.7 cells

Cited by 79 publications

References 39 publications

Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling

Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling

Activation of the Adenosine A₃Receptor in RAW 264.7 Cells Inhibits Lipopolysaccharide-Stimulated Tumor Necrosis Factor-α Release by Reducing Calcium-Dependent Activation of Nuclear Factor-κB and Extracellular Signal-Regulated Kinase 1/2

Calcium Channel Blockers Differentially Modulate Cytokine Production by Peripheral Blood Mononuclear Cells

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Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-κB activity in LPS-stimulated mouse peritoneal macrophages and RAW 264.7 cells

Cited by 79 publications

References 39 publications

Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling

Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling

Activation of the Adenosine A3Receptor in RAW 264.7 Cells Inhibits Lipopolysaccharide-Stimulated Tumor Necrosis Factor-α Release by Reducing Calcium-Dependent Activation of Nuclear Factor-κB and Extracellular Signal-Regulated Kinase 1/2

Calcium Channel Blockers Differentially Modulate Cytokine Production by Peripheral Blood Mononuclear Cells

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Product

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Activation of the Adenosine A₃Receptor in RAW 264.7 Cells Inhibits Lipopolysaccharide-Stimulated Tumor Necrosis Factor-α Release by Reducing Calcium-Dependent Activation of Nuclear Factor-κB and Extracellular Signal-Regulated Kinase 1/2