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PMID: 11207583, 8670890, 10051653
However, compelling evidence has emerged that IpaB and SipB are directly responsible for triggering apoptosis in macrophages through their ability to bind Caspase-1 (interleukin-1β converting enzyme; ICE), a member of the pro-apoptotic family of cysteine proteases ( Chen et al., 1996b; Hersh et al., 1999).
PMID: 11207583, 8670890, 10051653
However, compelling evidence has emerged that IpaB and SipB are directly responsible for triggering apoptosis in macrophages through their ability to bind Caspase-1 (interleukin-1β converting enzyme; ICE), a member of the pro-apoptotic family of cysteine proteases ( Chen et al., 1996b; Hersh et al., 1999).
indirect
PMID: 11207583, 9491891
Shigella-induced apoptosis does not require either Caspase-11, a caspase thought to be required for the activation of Caspase-1
indirect
PMID: 11207583
These findings have led to the hypothesis that delivery of IpaB/SipB to the macrophage cytosol stimulates the activation of Caspase-1, leading to the activation of the apoptotic machinery and, ultimately, the demise of the macrophage
indirect
PMID: 11207583
These findings have led to the hypothesis that delivery of IpaB/SipB to the macrophage cytosol stimulates the activation of Caspase-1, leading to the activation of the apoptotic machinery and, ultimately, the demise of the macrophage
indirect
PMID: 11207583, 1574116
An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1
indirect
PMID: 11207583, 1574116
An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1
indirect
PMID: 11207583, 1574116
An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1
indirect
PMID: 11207583, 1574116
An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1
indirect
PMID: 11207583, 9630225, 10362537
Salmonella and Shigella initiate the intracellular invasion process through the activation of the small Rho GTPases, which can induce localized actin rearrangements at the plasma membrane
indirect
PMID: 11207583, 9630225, 10362537
Salmonella and Shigella initiate the intracellular invasion process through the activation of the small Rho GTPases, which can induce localized actin rearrangements at the plasma membrane
indirectPMID: 11207583, 9548496, 8953049, 10224288
Activation of these GTPases stimulates the mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)
PMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
indirectPMID: 11207583, 9548496, 8953049, 10224288
Activation of these GTPases stimulates the mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)
PMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
indirectPMID: 11207583, 9548496, 8953049, 10224288
Activation of these GTPases stimulates the mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)
PMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 9548496
Activation of these MAPK signalling cascades by Salmonella leads to the phosphorylation and activation of the transcription factor AP-1
PMID: 11207583, 9363937, 9751057
CD14 co-operates with the recently identified family of Toll-like receptors (TLRs) in the recognition of conserved bacterial molecules or ‘pathogen-associated microbial patterns’ (PAMPs)
PMID: 11207583, 9363937, 9751057
CD14 co-operates with the recently identified family of Toll-like receptors (TLRs) in the recognition of conserved bacterial molecules or ‘pathogen-associated microbial patterns’ (PAMPs)
indirectPMID: 11207583
The results indicate that LPS alone is sufficient to stimulate the ERK kinase in macrophages, whereas ERK activation requires an effector from the Salmonella type III secretion system in epithelial cells
PMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
indirectPMID: 11207583
One role of IL-18 is to augment the induction of interferon (IFN)-γ, a cytokine produced mainly by T-cells and non-killer (NK) cells.
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
indirect
PMID: 11207583, 9548496
Activation of these MAPK signalling cascades by Salmonella leads to the phosphorylation and activation of the transcription factor AP-1
PMID: 11207583, 9548496
Activation of these MAPK signalling cascades by Salmonella leads to the phosphorylation and activation of the transcription factor AP-1
PMID: 11207583, 9081673
In addition to its role in activating cytokine expression, NF-κB can suppress apoptosis at least in part through the activation of several anti-apoptotic genes
PMID:11207583, 10488062
Before activation, the NF-κB transcription factor is sequestered within the cytoplasm by its interaction with two IκB ( Inhibitors of NF- κB) proteins, IκBα and IκBβ (for a review, see Karin, 1999). The IκB proteins bind to and prevent the recognition of NF-κB nuclear localization signals. Phosphorylation of the IκB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-κB to translocate to the nucleus and activate transcription
PMID:11207583, 10488062
Before activation, the NF-κB transcription factor is sequestered within the cytoplasm by its interaction with two IκB ( Inhibitors of NF- κB) proteins, IκBα and IκBβ (for a review, see Karin, 1999). The IκB proteins bind to and prevent the recognition of NF-κB nuclear localization signals. Phosphorylation of the IκB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-κB to translocate to the nucleus and activate transcription
indirect
PMID: 11207583, 9689033
Like AP-1, NF-κB can also be activated by MAPK pathways
indirect
PMID: 11207583, 9689033
Like AP-1, NF-κB can also be activated by MAPK pathways
indirect
PMID: 11207583, 9689033
Like AP-1, NF-κB can also be activated by MAPK pathways
PMID: 11207583, 10619864
This hypothesis has recently been complicated by evidence that Salmonella-induced NF-κB activation in epithelial cells occurs via a calcium-mediated signalling event
indirectPMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
indirectPMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
PMID:11207583, 9356502, 9294220, 9680199, 9916081
It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-α and IL-8
indirectPMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
indirectPMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
indirectPMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
PMID:11207583, 9356502, 9294220, 9680199, 9916081
It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-α and IL-8
indirectPMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-α
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
PMID:11207583, 9356502, 9294220, 9680199, 9916081
It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-α and IL-8
PMID:11207583, 10488062
Before activation, the NF-κB transcription factor is sequestered within the cytoplasm by its interaction with two IκB ( Inhibitors of NF- κB) proteins, IκBα and IκBβ (for a review, see Karin, 1999). The IκB proteins bind to and prevent the recognition of NF-κB nuclear localization signals. Phosphorylation of the IκB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-κB to translocate to the nucleus and activate transcription
indirect
PMID: 11207583, 9081673
In addition to its role in activating cytokine expression, NF-κB can suppress apoptosis at least in part through the activation of several anti-apoptotic genes
PMID: 11207583, 10489373
A recent report demonstrated that YopP/J binds to and prevents the activation of members of the MAP kinase kinase (MEK) superfamily (
indirectPMID: 11207583, 9529323, 9680199
The curious connection between the ability to suppress the synthesis of cytokines and the induction of apoptosis appears to hinge on the ability of YopP/J to inhibit the activation of the NF-κB transcription factor
PMID: 11207583, 9529323, 9680199, 10489373
One member of this family is IκB-kinase β (IKKβ), a protein implicated in the activation of NF-κB via phosphorylation of IκBs. Indeed, NF-κB activation is impaired in both macrophages and epithelial cells infected with wild-type but not YopP/J mutant YersiniaPMID: 11207583
Examples of PAMPs include LPS, BLPs, peptidoglycan and lipoteichoic acids.
PMID: 11207583
It has been shown that BLPs are the ligands for TLR-2
indirect
indirectPMID: 11207583, 9548496, 10415047
The induction of the chemokine IL-8 by Salmonella has been relatively well studied and requires the transcription factors NF-κB and AP-1
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
PMID:11207583, 9356502, 9294220, 9680199, 9916081
It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-α and IL-8
indirect
indirectPMID: 11207583, 9548496, 10415047
The induction of the chemokine IL-8 by Salmonella has been relatively well studied and requires the transcription factors NF-κB and AP-1
PMID: 11207583, 1287419, 8418045
It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-γ and TNF-α and that this inhibition is required for bacterial survival in animal models
PMID:11207583, 9356502, 9294220, 9680199, 9916081
It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-α and IL-8
PMID: 11207583
Examples of PAMPs include LPS, BLPs, peptidoglycan and lipoteichoic acids.
PMID: 11207583
Examples of PAMPs include LPS, BLPs, peptidoglycan and lipoteichoic acids.
indirectPMID: 11207583
The results indicate that LPS alone is sufficient to stimulate the ERK kinase in macrophages, whereas ERK activation requires an effector from the Salmonella type III secretion system in epithelial cells
PMID: 11207583, 9535085, 9188492
Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-γ and TNF-αPMID:11207583, 10488062
Before activation, the NF-κB transcription factor is sequestered within the cytoplasm by its interaction with two IκB ( Inhibitors of NF- κB) proteins, IκBα and IκBβ (for a review, see Karin, 1999). The IκB proteins bind to and prevent the recognition of NF-κB nuclear localization signals. Phosphorylation of the IκB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-κB to translocate to the nucleus and activate transcription
Inhibition of the proteasome with specific inhibitors (MG132)
results in the inhibition of NF-κB nuclear translocation, even in the presence of the proper activating stimuli.
PMID: 11207583, 9529323
This hypothesis is supported by the finding that the inhibition of NF-kB activation by the proteasome inhibitor MG-132 enables both LPS and plasmid-cured Yersinia to induce apoptosis in J774 macrophages (Ruckdeschel et al., 1998).
PMID: 11207583, 9237759, 9734363
Stimulation of TLRs with their cognate PAMPs is known to activate NF-κB through the phosphorylation of the IκB proteins
indirect
PMID: 11207583, 9237759, 9734363
Stimulation of TLRs with their cognate PAMPs is known to activate NF-κB through the phosphorylation of the IκB proteins
indirect
PMID: 11207583, 9237759, 9734363
Stimulation of TLRs with their cognate PAMPs is known to activate NF-κB through the phosphorylation of the IκB proteins
indirect
PMID: 11207583, 9237759, 9734363
Stimulation of TLRs with their cognate PAMPs is known to activate NF-κB through the phosphorylation of the IκB proteins
indirectPMID:11207583, 10488062
Before activation, the NF-κB transcription factor is sequestered within the cytoplasm by its interaction with two IκB ( Inhibitors of NF- κB) proteins, IκBα and IκBβ (for a review, see Karin, 1999). The IκB proteins bind to and prevent the recognition of NF-κB nuclear localization signals. Phosphorylation of the IκB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-κB to translocate to the nucleus and activate transcription
Inhibition of the proteasome with specific inhibitors (MG132)
results in the inhibition of NF-κB nuclear translocation, even in the presence of the proper activating stimuli.
PMID: 11207583, 9529323
This hypothesis is supported by the finding that the inhibition of NF-kB activation by the proteasome inhibitor MG-132 enables both LPS and plasmid-cured Yersinia to induce apoptosis in J774 macrophages (Ruckdeschel et al., 1998).PMID: 11207583
The results indicate that LPS alone is sufficient to stimulate the ERK kinase in macrophages, whereas ERK activation requires an effector from the Salmonella type III secretion system in epithelial cells