Furthermore, it blocked HMGB1 mediated TLR4 dependent signalling in vitro and circulating HMGB1 in vivo [XREF_BIBR].

We also briefly review the proposed use of TLR4 antagonists as antiviral treatments, including Eritoran, Resatorvid (CLI-095 and TAK242), and glycyrrhizin, as well as another compound, nifuroxazide, that interrupts TLR4 signalling.

TLR4 uses an accessory protein called MD2 for the recognition of LPS and viral proteins; MD2 initially binds to TLR4 within the cell and is also necessary for the correct trafficking of TLR4 to the cell surface [XREF_BIBR].

COVID-19 and Toll Like Receptor 4 (TLR4) : SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation.

We can confidently extrapolate the above findings in Sections 8.1 and 8.2 from SARS-CoV-1 to SARS-CoV-2; hence, we propose that SARS-CoV-2 would activate TLR4 directly, probably via its spike protein binding to TLR4 (and/or MD2).

This can be extrapolated to SARS-CoV-2, where intracellularly, its M protein may be inducing TLR4 dependent TRAF3 independent IFN-beta production.

Hence, a possible model for the interaction of SARS-CoV-2 and TLR4 is outlined in Section 11 and the graphical abstract (XREF_FIG) in which SARS-CoV-2 may activate TLR4 in the heart and lungs to cause aberrant TLR4 signalling in favour of the proinflammatory MyD88 dependent (canonical) pathway rather than the alternative TRIF and TRAM dependent anti-inflammatory and interferon pathway.

Moreover, HMGB1 and other DAMPS released from necrotic and lytic cells, as well as ambient LPS levels entering the lungs or released from opportunistic gram negative bacteria, can also activate TLR4, amplifying the already severe inflammation.

Specifically, the disulphide form of HMGB1 stimulates TLR4, while extracellular HMGB1 can form complexes with DNA, RNA, other DAMP or PAMP molecules; the complexes are endocytosed via RAGE and transported to the endolysosomal system.

A review by Andersson et al. suggests that HMGB1 released as a DAMP or secreted by activated immune cells could activate both TLR4 and the receptor for advanced glycation end-products (RAGE) to generate proinflammatory cytokines [XREF_BIBR].

IL-18 is also induced by the NLRP3 inflammasome in the lungs and heart.

Inhibition of the NLRP3 inflammasome signalling pathway downstream of TLR4 attenuates LPS induced acute lung injury [XREF_BIBR, XREF_BIBR].

This raises the question, is it only ACE2 that the spike protein of SARS-CoV-2 binds to or is there also another receptor involved, such as TLR4 which is known to promote cardiac hypertrophy, myocardial inflammation, and fibrosis [XREF_BIBR - XREF_BIBR]?

More relevantly, TLR4 is activated by viral PAMPs to initiate an innate immune and inflammatory response.

Inhibition of the NLRP3 inflammasome signalling pathway downstream of TLR4 attenuates LPS induced acute lung injury [XREF_BIBR, XREF_BIBR].

DAMP Mediated TLR4 Activation.

TLR4 activation by LPS on cardiomyocytes leads to subsequent reduction in myocardial contractility [XREF_BIBR, XREF_BIBR], and the predominant view in the literature is that TLR4 activation on cardiac structural fibroblasts and cardiac macrophages leads to a profibrotic and proinflammatory response, respectively [XREF_BIBR, XREF_BIBR].

Furthermore, while LPS increased TLR4 content in the lungs and heart by at least twofold, nifuroxazide was shown to significantly reduce TLR4 content by 45.7% in the lungs and 31.2% in the heart in the curative regimen and more so in the prophylactic regimen, compared to the LPS control [XREF_BIBR].

Additionally, it inhibited RSVF-, DENV-NS1-, and EBOV glycoprotein mediated TLR4 activation.

Mechanistically, LCZ696 prevents LPS induced activation of the TLR4 and Myd88 pathway and nuclear translocation of nuclear factor kappa-B (NF-kappaB) p65 factor.

Mechanistically, LCZ696 prevents LPS induced activation of the TLR4 and Myd88 pathway and nuclear translocation of nuclear factor kappa-B (NF-kappaB) p65 factor.

The priming step triggers nuclear factor-kappaB (NF-kappaB)-dependent upregulation of NLRP3 and pro-IL-1beta expression and lowers the activation threshold of NLRP3 by additional post-translational modification (PTMs).

NLRP3 activation is negatively regulated by tyrosine phosphorylation and protein tyrosine phosphatase non receptor 22 (PTPN22) dephosphorylates NLRP3 upon its activation.

This suggests that post-translational modifications of NLRP3 (such as phosphorylation and ubiquitination) and subsequent autophagic removal of inflammasome components upon their activation serves as a negative-feedback loop to prevent excessive inflammatory response.

Autophagic removal of NLRP3 inflammasome activators, such as intracellular DAMPs, NLRP3 inflammasome components, and cytokines can reduce inflammasome activation and inflammatory response.

Furthermore, silencing of NLRP3 or ASC in microglia suppressed caspase-1 activation and enhanced autophagy after PrP-106-126 stimulation.

As mentioned above, p62 expression negatively regulates NLRP3 activation by mediating mitophagic elimination of damaged mitochondria upon NLRP3 activation.

The pharmacological inhibition of autophagy and loss of p62 greatly enhanced the NLRP3 inflammasome activation.

NLRP3 activation is negatively regulated by tyrosine phosphorylation and protein tyrosine phosphatase non receptor 22 (PTPN22) dephosphorylates NLRP3 upon its activation.

Many of NLRP3 activators, such as nigericin, ATP, pore forming toxins, and particulate stimuli, are known to induce potassium efflux and decrease intracellular potassium levels, which is required for direct binding of NEK7 to NLRP3 inflammasome.

Furthermore, silencing of NLRP3 or ASC in microglia suppressed caspase-1 activation and enhanced autophagy after PrP-106-126 stimulation.

Downregulation of voltage dependent anion channels (VDAC), which are required for ROS production, or ROS scavengers impaired and reversed NLRP3 mediated caspase-1 activation and IL-1beta release in response to NLRP3 activators nigericin, MSU, alum, and silica.

Furthermore, a few other studies have shown that NLRP3 deficient mice have increased autophagy levels at baseline and under stress conditions, such as hypoxia or hyperoxia in different tissues and epithelial cells.

Furthermore, silencing of the NLRP3 downregulated autophagy and LC3-I conversion to LC3-II induced by MSU in osteoblasts.

Silencing core molecules of the NLRP3 inflammasome complex in human macrophages reduced the autophagy response after infection with Pseudomonas aeruginosa, however it enhanced the macrophage mediated killing of internalized P. aeruginosa.

NLRP3 was shown to modulate autophagy.

Autophagy Targets NLRP3 Inflammasome Components.

Downregulation of voltage dependent anion channels (VDAC), which are required for ROS production, or ROS scavengers impaired and reversed NLRP3 mediated caspase-1 activation and IL-1beta release in response to NLRP3 activators nigericin, MSU, alum, and silica.

The first hypothesis involves interaction between thioredoxin interacting protein (TXNIP) and NLRP3 after an increase in ROS caused by NLRP3 activators, such as MSU.

Mitochondrial dysfunction and release of mitochondrial ROS (mtROS) and mitochondrial DNA (mtDNA) are another important triggers for NLRP3 inflammasome activation and some of NLRP3 activators induce increased mtROS and cytosolic ROS generation.

Downregulation of voltage dependent anion channels (VDAC), which are required for ROS production, or ROS scavengers impaired and reversed NLRP3 mediated caspase-1 activation and IL-1beta release in response to NLRP3 activators nigericin, MSU, alum, and silica.

Even though the exact mechanism of NLRP3 inflammasome activation mediated by generation of mitochondrial ROS is not yet fully elucidated, several hypotheses have been suggested.

In the cytosol bacterial LPS activated caspase-4 and caspase-11 and induced pyroptosis and consequently activated NLRP3 inflammasome.

Growth Hormone Modulation of Hepatic Epidermal Growth Factor Receptor Signaling.

Growth Hormone Modulation of Hepatic Epidermal Growth Factor Receptor Signaling.

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).

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_FIG).

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).

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.

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.

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.

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.

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.

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.

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.

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 and MD2 complex but is independent of CD14 and LPS binding protein.

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.

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.

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 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.

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.

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.

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.

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.

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.

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

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.

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 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.

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.

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.

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.

In a follow-up paper, these researchers found that the NLRP3 inflammasome complex negatively regulated TLR4-TRIF-mediated autophagy by activating caspase-1-induced TRIF cleavage in response to PrP106-126 stimulation.

It consists of three main components : an apoptosis associated speck like protein containing a CARD (caspase activation and recruitment domain) (ASC), which functions as a central adaptor protein; an inflammatory caspase, caspase-1, and a pattern recognition receptor (PRR) protein, NLRP3 (nucleotide binding domain (NOD)-like receptor protein 3).

It consists of three main components : an apoptosis associated speck like protein containing a CARD (caspase activation and recruitment domain) (ASC), which functions as a central adaptor protein; an inflammatory caspase, caspase-1, and a pattern recognition receptor (PRR) protein, NLRP3 (nucleotide binding domain (NOD)-like receptor protein 3).