Skip to main content

Home/ Dr. Goodyear/ Group items tagged TLR4

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome - 0 views

www.ncbi.nlm.nih.gov/...PMC3099529

TLR toll-like receptors toll-like receptors fatty acids fat metabolic syndrome obesity overweight inflammation dietary

shared by Nathan Goodyear on 08 Oct 12 - No Cached
  • Activation of the innate immune system controls macronutrient metabolism
  • the innate immune response is the first line of defense against invading pathogens, wherein highly conserved pathogen-associated molecular patterns (PAMPs) are recognized by cognate pattern recognition receptors (PRRs
  • many studies have supported the idea that cytokine signaling directly promotes insulin resistance
  • ...10 more annotations...
  • innate immune system may be causally linked to obesity
  • adipose tissue contains a substantial population of macrophages, and macrophage-driven adipose inflammation contributes significantly to the pathogenesis of obesity
  • Collectively, activation of the innate immune system is strongly associated with ASCVD, insulin resistance, and obesity, and recent evidence suggests that much of this association can be traced to a unique family of PRRs known as TLRs
  • TLRs are a family of type I transmembrane receptors, currently thought to comprise at least 13 members in mammals, that specifically recognize a variety of microbial PAMPs and trigger host cellular responses
  • Free SFAs have indeed been demonstrated to elicit TLR4-dependent and TLR2-dependent responses in several cell types.
  • Endogenous SFAs released from adipocytes activate cocultured macrophages via TLR4 [18], indicating the potential for cellular crosstalk in adipose tissue. Collectively, there is a growing body of evidence that SFAs promote, whereas long chain PUFA antagonize, TLR4-dependent and TLR2-dependent signaling in multiple cell models
  • In an elegant study, Shi et al. [16] demonstrated that SFAs activate TLR4-dependent signaling in both macrophages and adipocytes, and mice lacking TLR4 are protected against insulin resistance driven by intravenous lipid infusion
  • In addition to effects in macrophages and adipocytes, SFAs can activate TLR4 in the hypothalamus, which triggers a central inflammatory response that results in resistance to anorexigenic signals
  • endogenous SFAs can indeed promote innate immunity and inflammatory disease
  • This finding strongly supports the work of Hwang and coworkers [19–22] demonstrating that ω-3 PUFAs can effectively counteract SFA-induced TLR4 activation in cultured macrophages and dendritic cells.
  • Nathan Goodyear on 08 Oct 12
     
    high dietary fatty acids linked to metabolic syndrome through TLR.
Nathan Goodyear

Inflammatory cause of metabolic syndrome via brain stress and NF-κB - 0 views

www.ncbi.nlm.nih.gov/...PMC3314172

metabolic syndrome TLR cytokines hypothalamus brain neurology metabolic syndrome NF-kappaB DIO diet induced obesity over nutrition nutrition inflammation

shared by Nathan Goodyear on 09 Jul 13 - No Cached
  • Mechanistic studies further showed that such metabolic inflammation is related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect under prolonged nutritional excess
  • intracellular stress-inflammation process for metabolic syndrome has been established in the central nervous system (CNS) and particularly in the hypothalamus
  • the CNS and the comprised hypothalamus are known to govern various metabolic activities of the body including appetite control, energy expenditure, carbohydrate and lipid metabolism, and blood pressure homeostasis
  • ...56 more annotations...
  • Reactive oxygen species (ROS) refer to a class of radical or non-radical oxygen-containing molecules that have high oxidative reactivity with lipids, proteins, and nucleic acids
  • a large measure of intracellular ROS comes from the leakage of mitochondrial electron transport chain (ETC)
  • Another major source of intracellular ROS is the intentional generation of superoxides by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
  • there are other ROS-producing enzymes such as cyclooxygenases, lipoxygenases, xanthine oxidase, and cytochrome p450 enzymes, which are involved with specific metabolic processes
  • To counteract the toxic effects of molecular oxidation by ROS, cells are equipped with a battery of antioxidant enzymes such as superoxide dismutases, catalase, peroxiredoxins, sulfiredoxin, and aldehyde dehydrogenases
  • intracellular oxidative stress has been indicated to contribute to metabolic syndrome and related diseases, including T2D [72; 73], CVDs [74-76], neurodegenerative diseases [69; 77-80], and cancers
  • intracellular oxidative stress is highly associated with the development of neurodegenerative diseases [69] and brain aging
  • dietary obesity was found to induce NADPH oxidase-associated oxidative stress in rat brain
  • mitochondrial dysfunction in hypothalamic proopiomelanocortin (POMC) neurons causes central glucose sensing impairment
  • Endoplasmic reticulum (ER) is the cellular organelle responsible for protein synthesis, maturation, and trafficking to secretory pathways
  • unfolded protein response (UPR) machinery
  • ER stress has been associated to obesity, insulin resistance, T2D, CVDs, cancers, and neurodegenerative diseases
  • brain ER stress underlies neurodegenerative diseases
  • under environmental stress such as nutrient deprivation or hypoxia, autophagy is strongly induced to breakdown macromolecules into reusable amino acids and fatty acids for survival
  • intact autophagy function is required for the hypothalamus to properly control metabolic and energy homeostasis, while hypothalamic autophagy defect leads to the development of metabolic syndrome such as obesity and insulin resistance
  • prolonged oxidative stress or ER stress has been shown to impair autophagy function in disease milieu of cancer or aging
  • TLRs are an important class of membrane-bound pattern recognition receptors in classical innate immune defense
  • Most hypothalamic cell types including neurons and glia cells express TLRs
  • overnutrition constitutes an environmental stimulus that can activate TLR pathways to mediate the development of metabolic syndrome related disorders such as obesity, insulin resistance, T2D, and atherosclerotic CVDs
  • Isoforms TLR1, 2, 4, and 6 may be particularly pertinent to pathogenic signaling induced by lipid overnutrition
  • hypothalamic TLR4 and downstream inflammatory signaling are activated in response to central lipid excess via direct intra-brain lipid administration or HFD-feeding
  • overnutrition-induced metabolic derangements such as central leptin resistance, systemic insulin resistance, and weight gain
  • these evidences based on brain TLR signaling further support the notion that CNS is the primary site for overnutrition to cause the development of metabolic syndrome.
  • circulating cytokines can limitedly travel to the hypothalamus through the leaky blood-brain barrier around the mediobasal hypothalamus to activate hypothalamic cytokine receptors
  • significant evidences have been recently documented demonstrating the role of cytokine receptor pathways in the development of metabolic syndrome components
  • entral administration of TNF-α at low doses faithfully replicated the effects of central metabolic inflammation in enhancing eating, decreasing energy expenditure [158;159], and causing obesity-related hypertension
  • Resistin, an adipocyte-derived proinflammatory cytokine, has been found to promote hepatic insulin resistance through its central actions
  • both TLR pathways and cytokine receptor pathways are involved in central inflammatory mechanism of metabolic syndrome and related diseases.
  • In quiescent state, NF-κB resides in the cytoplasm in an inactive form due to inhibitory binding by IκBα protein
  • IKKβ activation via receptor-mediated pathway, leading to IκBα phosphorylation and degradation and subsequent release of NF-κB activity
  • Research in the past decade has found that activation of IKKβ/NF-κB proinflammatory pathway in metabolic tissues is a prominent feature of various metabolic disorders related to overnutrition
  • it happens in metabolic tissues, it is mainly associated with overnutrition-induced metabolic derangements, and most importantly, it is relatively low-grade and chronic
  • this paradigm of IKKβ/NF-κB-mediated metabolic inflammation has been identified in the CNS – particularly the comprised hypothalamus, which primarily accounts for to the development of overnutrition-induced metabolic syndrome and related disorders such as obesity, insulin resistance, T2D, and obesity-related hypertension
  • evidences have pointed to intracellular oxidative stress and mitochondrial dysfunction as upstream events that mediate hypothalamic NF-κB activation in a receptor-independent manner under overnutrition
  • In the context of metabolic syndrome, oxidative stress-related NF-κB activation in metabolic tissues or vascular systems has been implicated in a broad range of metabolic syndrome-related diseases, such as diabetes, atherosclerosis, cardiac infarct, stroke, cancer, and aging
  • intracellular oxidative stress seems to be a likely pathogenic link that bridges overnutrition with NF-κB activation leading to central metabolic dysregulation
  • overnutrition is an environmental inducer for intracellular oxidative stress regardless of tissues involved
  • excessive nutrients, when transported into cells, directly increase mitochondrial oxidative workload, which causes increased production of ROS by mitochondrial ETC
  • oxidative stress has been shown to activate NF-κB pathway in neurons or glial cells in several types of metabolic syndrome-related neural diseases, such as stroke [185], neurodegenerative diseases [186-188], and brain aging
  • central nutrient excess (e.g., glucose or lipids) has been shown to activate NF-κB in the hypothalamus [34-37] to account for overnutrition-induced central metabolic dysregulations
  • overnutrition can present the cell with a metabolic overload that exceeds the physiological adaptive range of UPR, resulting in the development of ER stress and systemic metabolic disorders
  • chronic ER stress in peripheral metabolic tissues such as adipocytes, liver, muscle, and pancreatic cells is a salient feature of overnutrition-related diseases
  • recent literature supports a model that brain ER stress and NF-κB activation reciprocally promote each other in the development of central metabolic dysregulations
  • when intracellular stresses remain unresolved, prolonged autophagy upregulation progresses into autophagy defect
  • autophagy defect can induce NF-κB-mediated inflammation in association with the development of cancer or inflammatory diseases (e.g., Crohn's disease)
  • The connection between autophagy defect and proinflammatory activation of NF-κB pathway can also be inferred in metabolic syndrome, since both autophagy defect [126-133;200] and NF-κB activation [20-33] are implicated in the development of overnutrition-related metabolic diseases
  • Both TLR pathway and cytokine receptor pathways are closely related to IKKβ/NF-κB signaling in the central pathogenesis of metabolic syndrome
  • Overnutrition, especially in the form of HFD feeding, was shown to activate TLR4 signaling and downstream IKKβ/NF-κB pathway
  • TLR4 activation leads to MyD88-dependent NF-κB activation in early phase and MyD88-indepdnent MAPK/JNK pathway in late phase
  • these studies point to NF-κB as an immediate signaling effector for TLR4 activation in central inflammatory response
  • TLR4 activation has been shown to induce intracellular ER stress to indirectly cause metabolic inflammation in the hypothalamus
  • central TLR4-NF-κB pathway may represent one of the early receptor-mediated events in overnutrition-induced central inflammation.
  • cytokines and their receptors are both upstream activating components and downstream transcriptional targets of NF-κB activation
  • central administration of TNF-α at low dose can mimic the effect of obesity-related inflammatory milieu to activate IKKβ/NF-κB proinflammatory pathways, furthering the development of overeating, energy expenditure decrease, and weight gain
  • the physiological effects of IKKβ/NF-κB activation seem to be cell type-dependent, i.e., IKKβ/NF-κB activation in hypothalamic agouti-related protein (AGRP) neurons primarily leads to the development of energy imbalance and obesity [34]; while in hypothalamic POMC neurons, it primarily results in the development of hypertension and glucose intolerance
  • the hypothalamus, is the central regulator of energy and body weight balance [
  • Nathan Goodyear on 09 Jul 13
     
    Great article chronicles the biochemistry of "over nutrition" and inflammation through NF-kappaB activation and its impact on the brain.
Nathan Goodyear

Toll-Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Indu... - 0 views

circres.ahajournals.org/...1589.short

inflammation insulin resistance obesity FFA saturated fat TLR4 NF-kappaB IKK-Beta

shared by Nathan Goodyear on 21 Dec 11 - No Cached
  • Nathan Goodyear on 21 Dec 11
     
    high saturated fat intake (excess FFA) shown to contribute to obesity through TLR4 receptors.  TLR4 receptors are mediators in the innate immunity.   The result will be both IKK-Beta and NF-KappaB.
Nathan Goodyear

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk - 0 views

jme.endocrinology-journals.org/...R51.full

metabolic endotoxemia obesity insulin resistance cardiovascular disease LPS inflammation

shared by Nathan Goodyear on 04 Aug 14 - No Cached
  • Weight gain has been associated with a higher gut permeability
  • a high-fat diet promotes LPS absorption
  • higher concentrations of fatty acids impair intestinal barrier integrity
  • ...37 more annotations...
  • The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
  • TLRs are PRRs that recognize microbe-associated molecular patterns
  • TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
  • The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6, which are also elevated in obese and insulin-resistant patients
  • Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
  • Probiotics, prebiotics, and antibiotic treatment can reduce LPS absorption
  • LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
  • In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
  • In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
  • the gut microbiota has been recently proposed to be an environmental factor involved in the control of body weight and energy homeostasis by modulating plasma LPS levels
  • dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a bacterially related factor might be responsible for high-fat diet-induced obesity.
  • This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
  • n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
  • it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
  • this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
  • these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
  • This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can beneficially affect the host's weight and adiposity.
  • endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
  • in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
  • T2DM patients have mean values of LPS that are 76% higher than healthy controls
  • LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
  • LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
  • Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
  • The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
  • All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
  • LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
  • When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed, with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions such as obesity and metabolic syndrome
  • It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
  • On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
  • high-fat diet mice presented with ME, which positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and F4/80 (a specific marker of mature macrophages) mRNAs
  • prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
  • Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative stress, and macrophage infiltration markers
  • This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
  • high-fat feeding is associated with adipose tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
  • LPS has been shown to promote atherosclerosis
  • markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
  • As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
  • Nathan Goodyear on 04 Aug 14
     
    Very nice updated review on Metabolic endotoxemia
Nathan Goodyear

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals corre... - 0 views

www.ncbi.nlm.nih.gov/...PMC2833250

colon cancer colorectal cancer cancer LPS lipopolysaccharides

shared by Nathan Goodyear on 11 Sep 17 - No Cached
  • Nathan Goodyear on 11 Sep 17
     
    High TLR4 and MyD88 expression on the surface of colorectal cancer cells associated with increase liver mets potential and worsened prognosis.  LPS works through TLR4 and MyD88.
Nathan Goodyear

Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner - 0 views

www.ncbi.nlm.nih.gov/...PMC4185415

Chemotherapy "chemotherapy metastasis" metastasis cancer taxol

shared by Nathan Goodyear on 23 Jan 19 - No Cached
  • Nathan Goodyear on 23 Jan 19
     
    Taxol can promote tumor metastasis through TLR4 mechanism.
Nathan Goodyear

Antimalarial artesunate protects sepsis model mice against heat-killed Escherichia coli... - 0 views

www.ncbi.nlm.nih.gov/...18279792

Artesunate NF-kappaB cytokine storm TLR4 inflammation

shared by Nathan Goodyear on 07 Apr 20 - No Cached
  • Nathan Goodyear on 07 Apr 20
     
    Study finds that artesunate reduced TLR4 and TLR9 expression hindering LPS cytokine induction. The result was inhibition of NF-kappaB and IL-6 production.
Nathan Goodyear

(PDF) TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic repro... - 0 views

www.researchgate.net/...rom_lethal_influenza_infection

influenza cytokine storm TLR4 flu toll-like receptors

shared by Nathan Goodyear on 14 May 20 - No Cached
  • Nathan Goodyear on 14 May 20
     
    The point of this post is not the drug, but the fact that the inhibition of TLR4 blocked cytokine storm from influenza.
Nathan Goodyear

Elevated Muscle TLR4 Expression and Metabolic Endotoxemia in Human Aging - 0 views

www.ncbi.nlm.nih.gov/...PMC4311182

LPS Toll-like receptors toll like receptors TLR-4 metabolic endotoxemia TLR4

shared by Nathan Goodyear on 24 Jan 22 - No Cached
  • Nathan Goodyear on 24 Jan 22
     
    Not a direct cause and effect, but a clear associated between metabolic endotoxemia and increase in TLR4
Nathan Goodyear

Inflammation and insulin resistance 10.1016/j.febslet.2007.11.057 : FEBS Letters | Scie... - 0 views

www.sciencedirect.com/...S0014579307012082

inflammation insulin resistance IR PPAR TNF-alpha IL-6 IL-10 IL-1Beta JNK GLT-4 Resistin adiponectin Gherlin NF-kapppB iNOS lkkb obesity TLR-4

shared by Nathan Goodyear on 10 Jan 12 - No Cached
  • A subsequent study by Yuan et al. showed that Tnf treatment of 3T3L1 adipocytes induces insulin resistance and that this could be prevented by pretreatment of cells with aspirin
  • Activation of the Tnf receptor results in stimulation of NFκB signaling via Ikkb
  • Insulin is a pleiotropic hormone
  • ...25 more annotations...
  • the percentage of macrophages in a given adipose tissue depot is positively correlated with adiposity and adipocyte size
  • Il-10 is an anti-inflammatory cytokine produced by macrophages and lymphocytes
  • Il-10 exerts its anti-inflammatory activity by inhibiting Tnf-induced NFκB activation by reducing IKK activity [38]
  • adipose tissue macrophages are responsible for nearly all adipose tissue Tnf expression and a significant portion of Nos2 and Il6 expression
  • One theory holds that the expansion of adipose tissue leads to adipocyte hypertrophy and hyperplasia and that large adipocytes outstrip the local oxygen supply leading to cell autonomous hypoxia with activation of cellular stress pathways
  • The use of the anti-inflammatory compounds, salicylate and its derivative aspirin, for treating symptoms of T2DM dates back over 100 years
  • elevated levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin resistant states
  • overnutrition and obesity are often accompanied by elevations in tissue and circulating FFA concentrations, and saturated FFAs can directly activate pro-inflammatory responses
  • Adipokines such as resistin, leptin and adiponectin, which are secreted by adipocytes, can also affect inflammation and insulin sensitivity
  • In skeletal muscle insulin promotes glucose uptake by stimulating translocation of the GLUT4 glucose transporter
  • macrophages are also capable of undergoing a phenotypic switch from an M1 state, which was defined as the “classically activated” pro-inflammatory macrophage, to the M2 state or the “alternatively activated” non-inflammatory cell
  • saturated fatty acids are the most potent inducers of this inflammatory response
  • Several inducers of insulin resistance, including FFAs, pro-inflammatory cytokines and oxidative stress, activate the expression of Nos2, the gene that encodes iNOS (reviewed in [33]
  • Adipose tissue insulin signaling results in decreased hormone sensitive lipase activity and this anti-lipolytic effect inhibits free fatty acid (FFA) efflux out of adipocytes.
  • In the liver, insulin inhibits the expression of key gluconeogenic enzymes and, therefore, insulin resistance in liver leads to elevated hepatic glucose production
  • elevated JNK activity in liver, adipose tissue and skeletal muscle of obese insulin resistant mice, and knockout of Jnk1 (Jnk1−/−) leads to amelioration of insulin resistance in high fat diet
  • Adipose tissue from obese mice contains proportionately more M1 macrophages, whereas, lean adipose tissue contains more M2 macrophages, and increased M1 content positively correlates with inflammation, macrophage infiltration and insulin resistance
  • C-reactive protein (CRP)
  • these studies highlight the possibility that increased iNOS activity plays a direct role in the pathogenesis of insulin resistance
  • the important role of Ikkb in the development of obesity and inflammation-induced insulin resistance.
  • It is probable that local concentrations of inflammatory mediators, such as FFAs, Tnf or other cytokines/adipokines contribute to this polarity switch
  • Tnf and other cytokines/chemokines are symptomatic of inflammation, and while they propagate and/or maintain the inflammatory state, they are not the initial cause(s) of inflammation
  • Tlr4, in particular, is stimulated by lipopolysaccharide (LPS), an endotoxin released by gram-negative bacteria
  • Tlr4 belongs to the family of Toll-like receptors that function as pattern recognition receptors that guard against microorganismal infections as part of the innate immune system.
  • Tlr4 stimulation results in the activation of both Ikkb/NFκB and JNK/AP-1 signaling, culminating in the expression and secretion of pro-inflammatory cytokines/chemokines, including, Il1b, IL-6, Tnf, Mcp1, etc. (reviewed in [57
  • Nathan Goodyear on 10 Jan 12
     
    Great review of all the known components in the inflammation, insulin resistance link
Nathan Goodyear

Innate Immune Pathway Links Obesity to Insulin Resistance - 0 views

circres.ahajournals.org/...1531.full

insulin resistance FFA obesity innate immune system TLR4 NF-kappaB inflammation cytokines inflammatory

shared by Nathan Goodyear on 21 Dec 11 - No Cached
  • Nathan Goodyear on 21 Dec 11
     
    insulin resistance leads to excess FFA, obesity and activation of the innate immune signaling.  This uses TLR4  and stimulates NF-KappaB transcription.  The result is inflammation and associated inflammatory disease conditions.
Nathan Goodyear

Increased Toll-Like Receptor Activity in Patients With Metabolic Syndrome - 0 views

care.diabetesjournals.org/...dc11-2375

TLR4 TLR2 toll-like receptors inflammation metabolic syndrome MetS cytokines IL-1Beta IL-6 IL-8 TNF-alpha obesity overweight

shared by Nathan Goodyear on 29 Feb 12 - No Cached
  • Nathan Goodyear on 29 Feb 12
     
    TLR2 and TLR4 are increased in patients with metabolic syndrome.  No surprise that IL-1Beta, IL-6, IL-8, TNF-alpha were increased as well.
Nathan Goodyear

Anti-inflammatory effect of proteoglyca - PubMed Mobile - 0 views

www.ncbi.nlm.nih.gov/...22314502

progesterone LPS inflammation anti-inflammatory TLR4 BHRT HRT hormone hormones

shared by Nathan Goodyear on 07 Jun 12 - No Cached
  • Nathan Goodyear on 07 Jun 12
     
    progesterone inhibits LPS stimulated inflammation.  Progesterone actually inhibits TLR4 activation.  The statement that progesterone has no place in hormone therapy is both uneducated and uninformed.
Nathan Goodyear

Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells thro... - 0 views

onlinelibrary.wiley.com/...full

LPS lipopolysaccharides cancer pancreatic cancer

shared by Nathan Goodyear on 11 Sep 17 - No Cached
  • Nathan Goodyear on 11 Sep 17
     
    only abstract available here.  LPS increased pancreatic cancer cell invasion and progression through TLR4 and MyD88.
Nathan Goodyear

LPS-Induced TLR4 Signaling in Human Colorectal Cancer Cells Increases β1 Inte... - 0 views

cancerres.aacrjournals.org/...1989

cancer colon cancer colorectal cancer LPS lipopolysaccharides

shared by Nathan Goodyear on 11 Sep 17 - No Cached
  • Nathan Goodyear on 11 Sep 17
     
    cull culture study finds inhibition of LPS activated TLR4 in colorectal cancer cells decreased metastasis.
Nathan Goodyear

The role of infectious diseases in the catastrophic antiphospholipid syndrome - Science... - 1 views

www.sciencedirect.com/...S1568997215001585

cytokine storm toll-like receptors TLR4

shared by Nathan Goodyear on 14 May 20 - No Cached
  • Nathan Goodyear on 14 May 20
     
    Infectious diseases promote cytokine storm via TLR4 activation.
Nathan Goodyear

A TRIFfic Perspective on Acute Lung Injury: Cell - 0 views

www.cell.com/...S0092-8674(08)00454-6

toll-like receptors cytokine storm SARS pattern recognition receptors MERS IL-6 PRR TLR4

shared by Nathan Goodyear on 19 May 20 - No Cached
  • Nathan Goodyear on 19 May 20
     
    Recognition of TLR4 PRR involvement in cytokine storm from SARS all the way back to 2008. Md88 and TRIF involved.
Nathan Goodyear

SARS-CoV-2 spike protein interacts with and activates TLR41 | Cell Research - 0 views

www.nature.com/...s41422-021-00495-9

COVID19 SARS-CoV-2 SAR inflammation LPS COVID TLR4 TLR-4 COVID-19

shared by Nathan Goodyear on 05 Sep 21 - No Cached
  • Nathan Goodyear on 05 Sep 21
     
    "The induction of IL1B by trimeric spike proteins from SARS-CoV-2 or SARS-CoV was comparable to LPS treatment. Moreover, IL1B was induced by SARS-CoV-2, HCoV-229E and MHV-A59 via TLR4"
Nathan Goodyear

Lipopolysaccharide Causes an Increase in Intestinal Tight Junction Permeabili... - 0 views

www.ncbi.nlm.nih.gov/...PMC3562736

lipopolysaccharide metabolic endotoxemia TLR-4 leaky gut LPS TLR4 lipopolysaccharides

shared by Nathan Goodyear on 24 Jan 22 - No Cached
  • Nathan Goodyear on 24 Jan 22
     
    LPS increases break in tight junctions, leaky gut, to increase TLR4 expression and signaling.
Nathan Goodyear

Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative ... - 0 views

www.ncbi.nlm.nih.gov/...PMC5338938

NF-kapppB TLR-4 toll-like receptors inflammation NF-κB NF-KappaB toll like receptors metastasis TLRs TLR4 NFKB recurrence cancer

shared by Nathan Goodyear on 21 Jul 22 - No Cached
  • Nathan Goodyear on 21 Jul 22
     
    TLR4 promotes tumor progression, aggression, and resistance in ER-
1 - 20 of 70 Next › Last »
Showing 20▼ items per page