Together these data indicate that PPARgamma and Rev-erbalpha may inhibit NK-kappaB-dependent NLRP3 priming (XREF_FIG).

Indeed, while low extracellular Cl - enhances ATP induced IL-1beta secretion, high extracellular Cl - concentration or Cl - channel blockers inhibit NLRP3 activation.

For instance, ubiquitination of NLRP3 by FBXL12, TRIM1, ARIH2 or the dopamine induced E3 ligase MARCH7 promotes the proteasomal degradation of NLRP3 in resting macrophages, whereas deubiquitylation of NLRP3 LRR domain on K63 by BRCC3 triggers ASC oligomerization and inflammasome activation (XREF_FIG).

Interestingly, the bile acid receptor FXR is also able to physically interact with NLRP3 and Caspase1 thus inhibiting NLRP3 activity (XREF_FIG).

Furthermore, vitamin D enhances VDR mediated inhibition of NLRP3 activation.

Particularly, VDR has been shown to prevent NLRP3 modification on K63 and its subsequent activation.

Furthermore, vitamin D enhances VDR mediated inhibition of NLRP3 activation.

Since ROS scavengers attenuate NLRP3 activation, the generation of ROS was considered a common cellular response critical for NLRP3 activation.

In addition to caspase 1, cytosolic gram negative bacteria derived LPS may also be sensed independently of TLR4 signaling by human caspases 4 and 5, and mouse caspase 11, to induce the non canonical NLRP3 inflammasome.

In human hepatic hepG2 cell line, palmitic acid and LPS co-treatment induces the expression of NLRP3, NLRP6 and NLRP10 as well as Caspase 1 and IL-1beta.

In human hepatic hepG2 cell line, palmitic acid and LPS co-treatment induces the expression of NLRP3, NLRP6 and NLRP10 as well as Caspase 1 and IL-1beta.

For instance, ubiquitination of NLRP3 by FBXL12, TRIM1, ARIH2 or the dopamine induced E3 ligase MARCH7 promotes the proteasomal degradation of NLRP3 in resting macrophages, whereas deubiquitylation of NLRP3 LRR domain on K63 by BRCC3 triggers ASC oligomerization and inflammasome activation (XREF_FIG).

In addition, NLRP3 may also interact with mitochondrial antiviral signaling protein (MAVS), which is another mitochondrial outer MAM.

In addition, NLRP3 may also interact with mitochondrial antiviral-signaling protein (MAVS), which is another mitochondrial outer MAM ( xref – xref ).

Indeed, the LBD of VDR is able to physically interact with the NACHT-LRR domain of NLRP3 thus inhibiting the association of NLRP3 with BRCC3 and preventing NLRP3 deubiquitination ( xref ) ( xref ).

In addition, mtROS promotes Thioredoxin-interacting protein (TXNIP)-NLRP3 interaction involved in NLRP3 expression ( xref ) ( xref ).

Upon stimulation, NLRP3 oligomerizes through homotypic interactions between NACHT domains of two NLRP3 proteins and the subsequent recruitment of ASC through PYD-PYD interactions ( xref ).

For instance, the NLRP3 and Caspase1 complex is able to cleave GR, thus impairing glucocorticoid activity in acute lymphoblastic leukemia (ALL) patients.

In addition, vitD3 dampens ASC speck formation by preventing the NLRP3 and NEK7 interaction.

Regulation of NEK7-NLRP3 assembly is induced by ATP-driven potassium efflux ( xref ) but also in a K + -efflux independent manner ( xref ) and by reactive oxygen species (ROS) production ( xref ).

Interestingly, in addition to LPS, the pro atherogenic apolipoprotein ApoC3 is able to trigger TLR2 and TLR4 heterodimerization and promotes the alternative activation of NLRP3, thus mirroring the effect of oxLDL in the canonical activation of NLRP3.

Then, the ASC adaptor accumulates at Mitochondria associated ER membranes (MAMs) where the NLRP3 and ACS complex is formed.

Then, the ASC adaptor accumulates at Mitochondria-associated ER membranes (MAMs) where the NLRP3-ACS complex is formed ( xref ).

However, as HIF1alpha induces NLRP3 inflammasome activation, such regulatory mechanism may then account for LXR dependent activation of IL1-beta production in hypoxic atherosclerotic lesions.

Strikingly, ERbeta inhibits TNFalpha driven apoptosis and activates NLRP3 in endometriotic tissues.

Strikingly, ERβ inhibits TNFα-driven apoptosis and activates NLRP3 in endometriotic tissues ( xref ).

Remarkably, inhibition of the NLRP3 inflammasome pathway reduces liver inflammation and fibrosis in an experimental mouse NASH model.

Intriguingly, Berberine inhibits NLRP3 activation in DSS induced colitis in a Rev-erbalpha-dependent manner.

Although the source of NLRP3 activating ROS was controversial, the inhibition of the lysosomal NADPH oxidase did not alter NLRP3 activation in mouse and human cells, thus suggesting an alternative source of NLRP3 activating ROS, likely the mitochondria.

Interestingly, human LPS primed macrophages treated with ATRA exhibit elevated NLRP3 RNA and protein levels associated with an increase in caspase 1 and pro-IL-1beta maturation.

This signaling pathway relies on a cascade involving TLR4, TIR domain containing adapter molecule 1 (TRIF), RIPK1, FADD and caspase 8 that finally promotes NLRP3 activation.

The priming step has two main purposes : the transcriptional induction of the inflammasome complex components NLRP3, Caspase 1, IL-1beta, and IL-18 and the induction of post-translational modifications of NLRP3 (XREF_FIG).

Two recent reports demonstrated that chloride intracellular channels (CLICs), especially CLIC1 and CLIC4 mediate NLRP3 activation by promoting Cl - efflux downstream nigericin induced K + efflux and mitochondrial ROS production, which promotes CLIC translocation to the plasma membrane (XREF_FIG).

Indeed, treatment of BMDM with bile acids suppresses LPS and Nigericin mediated NLRP3 activation in a TGR5-cAMP-PKA dependent by inducing NLRP3 ubiquitination and phosphorylation.

Accordingly, aldosterone induced renal tubular cell injury by activating NLRP3 in a mtROS dependent manner.

Epleronone abolishes aldosterone induced NLRP3, ASC, Casp1, and IL-18 maturation in mouse kidney, but the mechanism is still uncovered.

In this context, aldosterone promotes mtROS production and subsequent NLRP3 activation.

Altogether, VDR inhibits NLRP3 inflammasome by favoring NLRP3 ubiquitination, preventing NLRP3 assembly and reducing ROS mediated NLRP3 activation.

Nevertheless, RORgamma deletion in LPS primed BMDM inhibits NLRP3 and IL-1beta secretion, which is consistent with a RORgamma inhibiting effect of SR1555 and SR2211 on these processes.

In addition, the thermal shift and co-immunoprecipitation assays revealed that oleuropein played an essential role in binding to the active sites of TLR4, as well as inhibiting TLR4 dimerization and suppressing the binding of TLR4 to MyD88.

In addition, the thermal shift and co-immunoprecipitation assays revealed that oleuropein played an essential role in binding to the active sites of TLR4, as well as inhibiting TLR4 dimerization and suppressing the binding of TLR4 to MyD88.

In addition, the thermal shift and co-immunoprecipitation assays revealed that oleuropein played an essential role in binding to the active sites of TLR4, as well as inhibiting TLR4 dimerization and suppressing the binding of TLR4 to MyD88.

In addition, the thermal shift and co-immunoprecipitation assays revealed that oleuropein played an essential role in binding to the active sites of TLR4, as well as inhibiting TLR4 dimerization and suppressing the binding of TLR4 to MyD88.

Thus, (i) individual EGFR induced signaling pathways have dissociable effects on NSPC proliferation, survival, and differentiation, (ii) activation of EGFR signaling is sufficient to stimulate qNSC cell cycle entry during early adulthood, and (iii) the proliferative effects of EGFR induced signaling are dominantly overridden by anti-proliferative signals associated with aging and Alzheimer 's disease.

Thus, (i) individual EGFR induced signaling pathways have dissociable effects on NSPC proliferation, survival, and differentiation, (ii) activation of EGFR signaling is sufficient to stimulate qNSC cell cycle entry during early adulthood, and (iii) the proliferative effects of EGFR induced signaling are dominantly overridden by anti-proliferative signals associated with aging and Alzheimer 's disease.

Pharmacological loss-of-function signaling experiments with cultured NSPCs revealed both overlap and selectivity in the biological functions modulated by the EGFR induced PI3K and AKT, MEK and ERK and mTOR signaling modules.

Pharmacological loss-of-function signaling experiments with cultured NSPCs revealed both overlap and selectivity in the biological functions modulated by the EGFR induced PI3K and AKT, MEK and ERK and mTOR signaling modules.

Meanwhile , GAS inhibited pyroptosis by downregulating NLRP3 , inflammatory factors ( IL-1beta , IL-18 ) and cleaved caspase-1 .

Meanwhile , GAS inhibited pyroptosis by downregulating NLRP3 , inflammatory factors ( IL-1beta , IL-18 ) and cleaved caspase-1 .

Moreover, MT inhibited the activation of the NF-kappaB pathway, and reduced the expression of inflammation related proteins (iNOS and COX-2), and pyroptosis related proteins (NLRP3, caspase-1, and GSDMD).

Moreover, MT inhibited the activation of the NF-kappaB pathway, and reduced the expression of inflammation related proteins (iNOS and COX-2), and pyroptosis related proteins (NLRP3, caspase-1, and GSDMD).

Neonatal mice deficient in TLR4 have markedly diminished LGR5+ stem cell proliferation and diminished crypt fission.

Neonatal mice deficient in TLR4 have decreased LGR5+ stem cell proliferation and crypt fission compared to wild type mice.

Low dose, high MW endogenous HA binding to TLR4 may preferentially promote PGE₂ production, whereas high dose low MW exogenous HA or LPS or LTA binding to TLR4 may preferentially promote CXCL12 production.

Low dose, high MW endogenous HA binding to TLR4 may preferentially promote PGE2 production, whereas high dose low MW exogenous HA or LPS or LTA binding to TLR4 may preferentially promote CXCL12 production.

TLR4 activation by LPS requires a TLR4 and MD2 complex, LPS binding protein, and CD14 which delivers LPS to the TLR4 and MD2 complex.

In contrast, TLR4 activation by LMW-HA requires a TLR4-MD2 complex but is independent of CD14 and LPS binding protein.

TLR4 activation by LPS requires a TLR4-MD2 complex, LPS binding protein, and CD14 which delivers LPS to the TLR4-MD2 complex ( xref , xref ).

In contrast, TLR4 activation by LMW-HA requires a TLR4 and MD2 complex but is independent of CD14 and LPS binding protein.

There is evidence that LMW-HA binds both CD44 and TLR4.

This may be the product of endogenous HAs of different molecular weights binding separately to CD44 and TLR4 or it may be the product of HA binding to a CD44-TLR4 complex ( xref , xref ).

This suggests that endogenous HA binding to both CD44 and TLR4 promotes intestinal growth.

This may be the product of endogenous HAs of different molecular weights binding separately to CD44 and TLR4 or it may be the product of HA binding to a CD44 and TLR4 complex.

Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE 2 production, which transactivates EGFR in LGR5+ crypt epithelial stem cells leading to increased proliferation.

TLR2 and TLR4 binding to LMW-HA promotes the production of proinflammatory cytokines including TNFα, MIP, IL-1β, IL-6, and IL-12 ( xref , xref – xref ).

Although most studies suggest that HMW-HA binds CD44 and LMW-HA binds TLR2 and TLR4.

TLR2 and TLR4 preferentially bind to LMW-HA.

This review addresses two novel related intercellular pathways in which a host molecule, HA, binding to TLR2 and TLR4 drives physiologic processes in the intestine and colon.

This suggests that endogenous HA binding to TLR2 and TLR4 blocks bleomycin-induced apoptosis.

Among the PAMPs are lipoteichoic acid (LTA), a component of gram positive bacteria that binds TLR2, and LPS, a component of gram negative bacteria that binds TLR4.

PGE₂ binding to EP2 blocks radiation-induced apoptosis by an AKT-EGFR mechanism ( xref ).

Although both LMW-HA and LPS bind to TLR4, the results of TLR4 activation by LMW-HA and LPS are not identical.

Low dose, high MW endogenous HA binding to TLR4 may preferentially promote PGE2 production, whereas high dose low MW exogenous HA or LPS or LTA binding to TLR4 may preferentially promote CXCL12 production.

HA binds to CD44, TLR2, TLR4, the receptor for HA mediated motility (RHAMM), layilin, lymphatic vessel endothelial HA receptor- 1 (LYVE-1), and HA receptor for endocytosis.

Low dose, high MW endogenous HA binding to TLR4 may preferentially promote PGE2 production, whereas high dose low MW exogenous HA or LPS or LTA binding to TLR4 may preferentially promote CXCL12 production.

The presence of CD44 also enhances the effects of HA binding to TLR4 although the presence of CD44 is not required for HA activation of TLR4.

EGFR can activate β-catenin via the receptor tyrosine kinase-PI3K-Akt pathway ( xref ).

EGFR can activate beta-catenin via the receptor tyrosine kinase-PI3K-Akt pathway.

Although the evidence suggests that EGFR activation in response to TLR4 signaling is mediated by PGE2, it is also possible that TLR4 signaling promotes EGFR activation through the production of amphiregulin, epiregulin or other EGFR ligands.

Administration of exogenous TLR2 or TLR4 agonists activates TLR2 and TLR4 on pericryptal macrophages inducing CXCL12 production with migration of cyclooxygenase2 expressing mesenchymal stem cells from the lamina propria of the villi to a site adjacent to LGR5+ epithelial stem cells.

This suggests that TLR2 and TLR4 signaling driven by PAMPs from commensal bacteria promotes epithelial proliferation during wound repair in the colon.

In contrast to wound repair, where inflammation accompanies enhanced epithelial proliferation driven by TLR2 and TLR4 activation, in intestinal growth TLR4 activation promotes epithelial proliferation in the absence of inflammation.

Administration of exogenous TLR2 or TLR4 agonists activates TLR2 and TLR4 on pericryptal macrophages inducing CXCL12 production with migration of cyclooxygenase2 expressing mesenchymal stem cells from the lamina propria of the villi to a site adjacent to LGR5+ epithelial stem cells.

In contrast , in adult mice TLR2 / TLR4 activation on pericryptal macrophages by exogenous HA or other TLR2 / TLR4 agonists results in CXCL12 production resulting in the migration of COX-2 expressing MSCs .

TLR4 activation by LPS and LMW-HA require different accessory molecules.

Although both LMW-HA and LPS bind to TLR4, the results of TLR4 activation by LMW-HA and LPS are not identical.

TLR4 activation by LPS requires a TLR4 and MD2 complex, LPS binding protein, and CD14 which delivers LPS to the TLR4 and MD2 complex.

TLR4 activation by LPS requires a TLR4-MD2 complex , LPS binding protein , and CD14 which delivers LPS to the TLR4-MD2 complex ( 33 , 34 ) .

TLR4 activation by LPS and LMW-HA require different accessory molecules .

Although both LMW-HA and LPS bind to TLR4 , the results of TLR4 activation by LMW-HA and LPS are not identical .

Activation of TLR2 by LTA or activation of TLR4 by LPS or HA results in the release of the chemokine CXCL12 , which binds to CXCR4 on COX-2 expressing MSCs .

In this pathway, TLR4, which is usually associated with innate immunity, is activated not by the microbial product LPS, but by HA, a host molecule.

In human biliary carcinoma cells in vitro, addition of LPS initiates a positive feedback loop of TLR4 activation, PGE2 production through COX-2 and EGFR activation.

Although there are differences in the accessory molecules involved in TLR4 activation by LPS and LMW - HA , TLR4 activation by either one promotes wound healing ( 12 , 27 , 28 , 33 ) .

TLR4 activation by HA also affects the immune response in ischemia- reperfusion injury in the kidney and in acute allograft rejection in a skin transplant model.

Although there are differences in the accessory molecules involved in TLR4 activation by LPS and LMW- HA, TLR4 activation by either one promotes wound healing ( xref , xref , xref , xref ).

TLR4 activation by HA also affects the immune response in ischemia- reperfusion injury in the kidney and in acute allograft rejection in a skin transplant model ( xref ).

The presence of CD44 also enhances the effects of HA binding to TLR4 although the presence of CD44 is not required for HA activation of TLR4.

In the first pathway ( xref ), intestinal and colonic growth is regulated by endogenous HA activating TLR4 on pericryptal macrophages resulting in the release of PGE₂ which promotes LGR5+ stem cell proliferation, crypt fission and intestinal elongation.

This suggests that TLR4 activation by endogenous HA promotes healing in DSS colitis.

TLR4 activation by HA also plays a role in wound repair ( xref ).

Despite these suggestions there is good evidence that endogenous HA activates TLR4 and promotes growth even though most of the endogenous HA is in the high MW form ( xref , xref , xref ).

In mice deficient in TLR4, PEP-1 does not further reduce LGR5+ stem cell proliferation or crypt fission suggesting that TLR4 activation by endogenous HA drives LGR5+ stem cell proliferation and crypt fission.

TLR4 activation by HA drives LGR5+ epithelial stem cell proliferation and crypt fission in normal growth in the intestine and colon ( xref , xref ).

A study of pulmonary injury induced by intratracheal bleomycin demonstrates the role of HA activation of TLR4 in sterile injury ( xref ).

In the first pathway (XREF_FIG), intestinal and colonic growth is regulated by endogenous HA activating TLR4 on pericryptal macrophages resulting in the release of PGE2 which promotes LGR5+ stem cell proliferation, crypt fission and intestinal elongation.

A study of pulmonary injury induced by intratracheal bleomycin demonstrates the role of HA activation of TLR4 in sterile injury.

Taken together these studies addressing the cellular location of the TLR4 signaling that drives growth and wound repair and the nature of the relevant TLR4 ligand suggest that HA activation of myeloid TLR4 mediates intestinal and colonic growth and wound repair.

This suggests that TLR4 activation by endogenous HA promotes healing in DSS colitis.

TLR4 activation by HA also plays a role in wound repair.

Despite these suggestions there is good evidence that endogenous HA activates TLR4 and promotes growth even though most of the endogenous HA is in the high MW form.

There are suggestions that TLR4 is preferentially activated by the low MW form of HA.

TLR4 activation by HA drives LGR5+ epithelial stem cell proliferation and crypt fission in normal growth in the intestine and colon.

The presence of CD44 also enhances the effects of HA binding to TLR4 although the presence of CD44 is not required for HA activation of TLR4.

TLR2 and TLR4 activation by HA mediates wound repair in the bleomycin model of lung injury.

Wound repair mediated by HA activation of TLR2 and TLR4 is also seen in the lung.

In this pathway, TLR4, which is usually associated with innate immunity, is activated not by the microbial product LPS, but by HA, a host molecule.

TLR4 activation by HA also plays a role in wound repair ( 22 ) .

TLR4 activation by HA also affects the immune response in ischemia - reperfusion injury in the kidney and in acute allograft rejection in a skin transplant model ( 8) .

Moreover , in contrast to wound repair where activation of TLRs by both microbial PAMPs and non-microbial agents , such as HA , play a role ( 11 , 12 ) , intestinal growth is driven only by TLR4 activation by the nonmicrobial agent , HA ( 17 ) .

Based on the growth studies, it is likely that EGFR activation by PGE2 is also the mechanism of the increased epithelial proliferation in the repair phase of DSS colitis.

In growth EGFR activation by PGE2 accounts for about 30% of LGR5+ cell proliferation.

Although the evidence suggests that EGFR activation in response to TLR4 signaling is mediated by PGE2, it is also possible that TLR4 signaling promotes EGFR activation through the production of amphiregulin, epiregulin or other EGFR ligands.

Here, we demonstrate that epidermal growth factor receptor (EGFR) activation induces AKT dependent PCK1 pS90, PCK1 mediated INSIG1 pS207 and INSIG2 pS151, and nuclear SREBP1 accumulation in NSCLC cells.

Here, we demonstrate that epidermal growth factor receptor (EGFR) activation induces AKT dependent PCK1 pS90, PCK1 mediated INSIG1 pS207 and INSIG2 pS151, and nuclear SREBP1 accumulation in NSCLC cells.

XREF_BIBR Cl - channel blockers such as mefenamic acid, flufenamic acid, benzoic acid, etc, can inhibit the NLRP3 activation.

XREF_BIBR Cl - channel blockers such as mefenamic acid, flufenamic acid, benzoic acid, etc, can inhibit the NLRP3 activation.

XREF_BIBR The molecular interaction of NLRP3 and MAVS in DCs infected with RVFV was observed by confocal microscopy.

It was also observed that viral replication was vital for the processing of IL-1β. xref The mitochondrial protein MAVS directly interacts with NLRP3 and also influences IL-1β secretion in response to various NLRP3 activators (eg SeV V protein). xref The molecular interaction of NLRP3 and MAVS in DCs infected with RVFV was observed by confocal microscopy. xref Thus, RVFV brings about the release of IL-1β by activating the NLRP3 inflammasome.

XREF_BIBR The molecular interaction of NLRP3 and MAVS in DCs infected with RVFV was observed by confocal microscopy.

It was also observed that viral replication was vital for the processing of IL-1β. xref The mitochondrial protein MAVS directly interacts with NLRP3 and also influences IL-1β secretion in response to various NLRP3 activators (eg SeV V protein). xref The molecular interaction of NLRP3 and MAVS in DCs infected with RVFV was observed by confocal microscopy. xref Thus, RVFV brings about the release of IL-1β by activating the NLRP3 inflammasome.

XREF_BIBR It is a non segmented RNA virus that encodes phosphoprotein (P), protein V, and protein C. XREF_BIBR MV activates NLRP3 inflammasomes, which leads to caspase-1-mediated production of mature IL-1beta.

XREF_BIBR IL- 1beta secretion was assessed in THP-1 cells after using short hairpin RNA to target human NLRP3, which indicated that MV activates NLRP3 inflammasomes.

XREF_BIBR Thus, MV infection can activate NLRP3 and cause IL-1beta secretion.

XREF_BIBR It is a non segmented RNA virus that encodes phosphoprotein (P), protein V, and protein C. XREF_BIBR MV activates NLRP3 inflammasomes, which leads to caspase-1-mediated production of mature IL-1beta.

XREF_BIBR IL- 1beta secretion was assessed in THP-1 cells after using short hairpin RNA to target human NLRP3, which indicated that MV activates NLRP3 inflammasomes.

XREF_BIBR Thus, MV infection can activate NLRP3 and cause IL-1beta secretion.

XREF_BIBR It can induce the cleavage of pro-IL-1beta by caspase-1 and the subsequent release of IL-1beta, which involves activating NLRP3 inflammasomes.

XREF_BIBR, XREF_BIBR M protein of DENV is responsible for endothelial dysfunction, and vascular leakage resulting in IL-1beta mediated NLRP3 activation.

IL-1beta production was significantly higher in ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice, resulting in NLRP3 involvement M mediated IL-1beta production and secretion.

XREF_BIBR It can induce the cleavage of pro-IL-1beta by caspase-1 and the subsequent release of IL-1beta, which involves activating NLRP3 inflammasomes.

XREF_BIBR, XREF_BIBR M protein of DENV is responsible for endothelial dysfunction, and vascular leakage resulting in IL-1beta mediated NLRP3 activation.

IL-1beta production was significantly higher in ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice, resulting in NLRP3 involvement M mediated IL-1beta production and secretion.

XREF_BIBR However, some other studies show that mitochondrial MAVS activate NLRP3 inflammasome in presence of RNA viruses but not non viral stimuli such as ATP or nigericin.

The ROS model xref represents a common pathway underlying NLRP3 inflammasome activation. xref Mitochondria are the main intracellular organelles that produce ROS. xref Nigericin, asbestos, silica, and alum induce ROS production, and ROS is generated by NADPH oxidase. xref ROS leads to K + fluxes, activating the NLRP3 inflammasome. xref , xref However, ROS inhibitors manipulate the priming modulation of NLRP3 as used in large concentration. xref Again, mitochondrial DNA release can occur downstream activation of NLRP3. xref Another study reported that mitochondria-associated adaptor MAVS can activatedNLRP3 inflammasome in presence of soluble stimuli such as ATP, nigericin but not particulate matter such as alum or monosodium urate. xref However, some other studies show that mitochondrial MAVS activate NLRP3 inflammasome in presence of RNA viruses but not non-viral stimuli such as ATP or nigericin. xref , xref RNA virus such as murine norovirus (MNV) leads to Gasdermin D (GSDSD) dependent pyroptosis resulting NLRP3 activation in STAT-1 deficient macrophages displayed increased MAVS mediated IL-1β secretion. xref Additionally, Mitofusin-2, an outer membrane protein of mitochondria-responsible for mitochondrial fusion is required for NLRP3 activation after infection with RNA viruses such as influenza, measles or encephalomyocarditis virus (EMCV). xref Still there is a need for deep research to unveil the exact mechanism of mitochondrial effect in NLRP3 activation.

XREF_BIBR However, some other studies show that mitochondrial MAVS activate NLRP3 inflammasome in presence of RNA viruses but not non viral stimuli such as ATP or nigericin.

The ROS model xref represents a common pathway underlying NLRP3 inflammasome activation. xref Mitochondria are the main intracellular organelles that produce ROS. xref Nigericin, asbestos, silica, and alum induce ROS production, and ROS is generated by NADPH oxidase. xref ROS leads to K + fluxes, activating the NLRP3 inflammasome. xref , xref However, ROS inhibitors manipulate the priming modulation of NLRP3 as used in large concentration. xref Again, mitochondrial DNA release can occur downstream activation of NLRP3. xref Another study reported that mitochondria-associated adaptor MAVS can activatedNLRP3 inflammasome in presence of soluble stimuli such as ATP, nigericin but not particulate matter such as alum or monosodium urate. xref However, some other studies show that mitochondrial MAVS activate NLRP3 inflammasome in presence of RNA viruses but not non-viral stimuli such as ATP or nigericin. xref , xref RNA virus such as murine norovirus (MNV) leads to Gasdermin D (GSDSD) dependent pyroptosis resulting NLRP3 activation in STAT-1 deficient macrophages displayed increased MAVS mediated IL-1β secretion. xref Additionally, Mitofusin-2, an outer membrane protein of mitochondria-responsible for mitochondrial fusion is required for NLRP3 activation after infection with RNA viruses such as influenza, measles or encephalomyocarditis virus (EMCV). xref Still there is a need for deep research to unveil the exact mechanism of mitochondrial effect in NLRP3 activation.

The V protein binds to the C-terminal domain of NLRP3 to prevent NLRP3 mediated IL-1beta secretion.

After FMDV infection, activated NLRP3 induces IL-1beta secretion, independent of the RIG-1 inflammasome.

The V protein binds to the C-terminal domain of NLRP3 to prevent NLRP3 mediated IL-1beta secretion.

After FMDV infection, activated NLRP3 induces IL-1beta secretion, independent of the RIG-1 inflammasome.

Recent research demonstrated that, during certain pathogen infections, NLRP3 is able to detect specific ligands, activate caspase-1, and induce the release of various pro inflammatory cytokines with major roles against viral infection.

XREF_BIBR Infecting NLRP3 transfected cells with SeV led to NLRP3 mediated caspase-1 activation, but this did not occur in the absence of NLRP3.

These results indicate that SeV infection leads to NLRP3-dependent caspase-1 activation. xref SeV infection of THP-1 cells caused caspase-1 activation and IL-1β secretion, while SeV infection of MAVS-knockdown THP-1 cells significantly decreased the formation of active caspase-1 and the mature form of IL-1β (p17).

Recent research demonstrated that, during certain pathogen infections, NLRP3 is able to detect specific ligands, activate caspase-1, and induce the release of various pro inflammatory cytokines with major roles against viral infection.

XREF_BIBR Infecting NLRP3 transfected cells with SeV led to NLRP3 mediated caspase-1 activation, but this did not occur in the absence of NLRP3.

These results indicate that SeV infection leads to NLRP3-dependent caspase-1 activation. xref SeV infection of THP-1 cells caused caspase-1 activation and IL-1β secretion, while SeV infection of MAVS-knockdown THP-1 cells significantly decreased the formation of active caspase-1 and the mature form of IL-1β (p17).

XREF_BIBR NLRP3 Inflammasome activation enables homeostasis restoration after traumatic tissue damage by promoting damage clearance, tissue recovery and regeneration.

XREF_BIBR NLRP3 Inflammasome activation enables homeostasis restoration after traumatic tissue damage by promoting damage clearance, tissue recovery and regeneration.

XREF_BIBR Above all data prove that HCV induced NLRP3 inflammasome activation in potassium efflux and ROS dependent manner.

XREF_BIBR Above all data prove that HCV induced NLRP3 inflammasome activation in potassium efflux and ROS dependent manner.

XREF_BIBR Above all data prove that HCV induced NLRP3 inflammasome activation in potassium efflux and ROS dependent manner.

XREF_BIBR Above all data prove that HCV induced NLRP3 inflammasome activation in potassium efflux and ROS dependent manner.

Notably, Nek7 as an undisputed essential positive regulator which is required for the stimuli or ion channel mediated NLRP3 inflammasome activation.

Notably, Nek7 as an undisputed essential positive regulator which is required for the stimuli or ion channel mediated NLRP3 inflammasome activation.

NLRP3 was activated by ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice.

NLRP3 was activated by ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice.

NLRP3 was activated by ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice.

NLRP3 was activated by ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice.

XREF_BIBR Mechanically, the NA + inflow modulated the activation of NLRP3 partly by minimizing the decrease in intracellular K+.

XREF_BIBR Mechanically, the NA + inflow modulated the activation of NLRP3 partly by minimizing the decrease in intracellular K+.

This creates an ionic imbalance, leading to K + efflux combined with Na + efflux, and ROS production, which activates the NLRP3 inflammasome.

Another study showed that mitochondrial ROS can induce NLRP3 inflammasome activation.

This creates an ionic imbalance, leading to K + efflux combined with Na + efflux, and ROS production, which activates the NLRP3 inflammasome.

Another study showed that mitochondrial ROS can induce NLRP3 inflammasome activation.

XREF_BIBR DENV M mediated vascular permeability and leakage was confirmed by infecting BMDMs with lentivirus-M isolated from NLRP3 +/+ and NLRP3 -/- mice and treated with LPS plus ATP or LPS plus nigericin.

NLRP3 was activated by ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice.

XREF_BIBR Another study proves that CASR and GPRC6A are only necessary to activate the extracellular Ca 2+ NLRP3 activation and not to activate ATP induced NLRP3.

XREF_BIBR DENV M mediated vascular permeability and leakage was confirmed by infecting BMDMs with lentivirus-M isolated from NLRP3 +/+ and NLRP3 -/- mice and treated with LPS plus ATP or LPS plus nigericin.

NLRP3 was activated by ATP or nigericin in lentivirus-M-treated BMDMs of NLRP3 +/+ mice.

XREF_BIBR Another study proves that CASR and GPRC6A are only necessary to activate the extracellular Ca 2+ NLRP3 activation and not to activate ATP induced NLRP3.

Notably, Nek7 as an undisputed essential positive regulator which is required for the stimuli or ion channel mediated NLRP3 inflammasome activation.

Notably, Nek7 as an undisputed essential positive regulator which is required for the stimuli or ion channel mediated NLRP3 inflammasome activation.

XREF_BIBR Again, PB1-F2 protein of highly pathogenic influenza A (H7N9) seized the IL-1beta secretion from IAV infected macrophages resulting the inhibition of RNA induced NLRP3 inflammasome activation.

XREF_BIBR Again, PB1-F2 protein of highly pathogenic influenza A (H7N9) seized the IL-1beta secretion from IAV infected macrophages resulting the inhibition of RNA induced NLRP3 inflammasome activation.

XREF_BIBR It was reported that Sars-CoV 3A viroporin could induce the NLRP3 inflammasome activation and IL-1beta production via mitochondrial ROS and ion channel.

It proves that Sars-Cov 3A viroporin activates NLRP3 inflammasome by K + channel.

However, Mito-TEMPO treated BMDMs shows a lower secretion of 3A viroporin mediated IL-1beta, indicating that mitochondrial ROS is essential for Sars-Cov 3A viroporin mediated NLRP3 activation.

XREF_BIBR All of these data prove that Sars-Cov 3A viroporin can activate NLRP3 inflammasome via mitochondrial ROS and K + channel.

XREF_BIBR It was reported that Sars-CoV 3A viroporin could induce the NLRP3 inflammasome activation and IL-1beta production via mitochondrial ROS and ion channel.

It proves that Sars-Cov 3A viroporin activates NLRP3 inflammasome by K + channel.

However, Mito-TEMPO treated BMDMs shows a lower secretion of 3A viroporin mediated IL-1beta, indicating that mitochondrial ROS is essential for Sars-Cov 3A viroporin mediated NLRP3 activation.

XREF_BIBR All of these data prove that Sars-Cov 3A viroporin can activate NLRP3 inflammasome via mitochondrial ROS and K + channel.

NLRP3 inflammasome mediated cytokine production and pyroptosis cell death in breast cancer.

NLRP3 inflammasome mediated cytokine production and pyroptosis cell death in breast cancer.

Pharmacologic CREB1 inhibition dramatically reduced FOXA1 and B-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic KRAS and mutant p53 to mitigate metastasis.

Pharmacologic CREB1 inhibition dramatically reduced FOXA1 and B-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic KRAS and mutant p53 to mitigate metastasis.

Specifically, mutant p53 and CREB1 upregulate the pro metastatic, pioneer transcription factor, FOXA1, activating its transcriptional network while promoting Wnt and B-catenin signaling, together driving PDAC metastasis.

Specifically, mutant p53 and CREB1 upregulate the pro metastatic, pioneer transcription factor, FOXA1, activating its transcriptional network while promoting Wnt and B-catenin signaling, together driving PDAC metastasis.

Interestingly, although NLRP3 deletion and caspase-1 inhibition appears to protect against amyloid induced AD like disease, IL-18 deletion did not protect APP and PS1 mice.