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-1¦Â converting enzyme; ICE), a member of the pro-apoptotic family of cysteine proteases ( Chen et al., 1996b; Hersh et al., 1999).

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â 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

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

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

PMID: 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-¦Ã and TNF-¦Á

PMID: 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-¦Ã and TNF-¦Á

PMID: 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-¦Ã and TNF-¦Á

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, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription Inhibition of the proteasome with specific inhibitors (MG132) results in the inhibition of NF-¦ÊB 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

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-1¦Â converting enzyme; ICE), a member of the pro-apoptotic family of cysteine proteases ( Chen et al., 1996b; Hersh et al., 1999).

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 ¡Æpathogen-associated microbial patterns¡Ç (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 ¡Æpathogen-associated microbial patterns¡Ç (PAMPs)

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 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-¦Ã and TNF-¦Á

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

PMID: 11207583, 9689033 Like AP-1, NF-¦ÊB can also be activated by MAPK pathways

PMID: 11207583, 9689033 Like AP-1, NF-¦ÊB can also be activated by MAPK pathways

PMID: 11207583, 9491891 Shigella-induced apoptosis does not require either Caspase-11, a caspase thought to be required for the activation of Caspase-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, 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-¦ÊB can suppress apoptosis at least in part through the activation of several anti-apoptotic genes

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription

PMID: 11207583, 9689033 Like AP-1, NF-¦ÊB can also be activated by MAPK pathways

PMID: 11207583, 10619864 This hypothesis has recently been complicated by evidence that Salmonella-induced NF-¦ÊB activation in epithelial cells occurs via a calcium-mediated signalling event

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-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

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

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-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á 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-¦Á and IL-8

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-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

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-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

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-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á 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-¦Á and IL-8

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-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á 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-¦Á and IL-8

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription

PMID: 11207583, 9081673 In addition to its role in activating cytokine expression, NF-¦ÊB 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 (

PMID: 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-¦ÊB transcription factor PMID: 11207583, 9529323, 9680199, 10489373 One member of this family is I¦ÊB-kinase ¦Â (IKK¦Â), a protein implicated in the activation of NF-¦ÊB via phosphorylation of I¦ÊBs. Indeed, NF-¦ÊB activation is impaired in both macrophages and epithelial cells infected with wild-type but not YopP/J mutant Yersinia

PMID: 11207583, 9548496, 10415047 The induction of the chemokine IL-8 by Salmonella has been relatively well studied and requires the transcription factors NF-¦ÊB and AP-1 PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á 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-¦Á and IL-8

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

PMID: 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

PMID: 11207583, 9548496, 10415047 The induction of the chemokine IL-8 by Salmonella has been relatively well studied and requires the transcription factors NF-¦ÊB and AP-1 PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á 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-¦Á 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.

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 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-¦Ã and TNF-¦Á

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription Inhibition of the proteasome with specific inhibitors (MG132) results in the inhibition of NF-¦ÊB 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, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â 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

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â 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

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â 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

PMID: 11207583 One role of IL-18 is to augment the induction of interferon (IFN)-¦Ã, 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-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models