scholarly journals Appetite Regulation of TLR4-Induced Inflammatory Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Yongxiang Li ◽  
Qingyan Jiang ◽  
Lina Wang
Keyword(s):  
Therapeutic Interventions ◽  
Appetite Regulation ◽  
Toll Like Receptor ◽  
Inflammatory Signaling ◽  
Toll Like Receptor 4 ◽  
Inflammatory Conditions ◽  
Normal Metabolism ◽  
Key Issues ◽  
Dopamine Signaling ◽  
The Brain

Appetite is the basis for obtaining food and maintaining normal metabolism. Toll-like receptor 4 (TLR4) is an important receptor expressed in the brain that induces inflammatory signaling after activation. Inflammation is considered to affect the homeostatic and non-homeostatic systems of appetite, which are dominated by hypothalamic and mesolimbic dopamine signaling. Although the pathological features of many types of inflammation are known, their physiological functions in appetite are largely unknown. This review mainly addresses several key issues, including the structures of the homeostatic and non-homeostatic systems. In addition, the mechanism by which TLR4-induced inflammatory signaling contributes to these two systems to regulate appetite is also discussed. This review will provide potential opportunities to develop new therapeutic interventions that control appetite under inflammatory conditions.

scholarly journals Lack of Lipid A Pyrophosphorylation and FunctionallptAReduces Inflammation by Neisseria Commensals

2012 ◽  
Vol 80 (11) ◽  
pp. 4014-4026 ◽  
Author(s):  
Constance M. John ◽  
Mingfeng Liu ◽  
Nancy J. Phillips ◽  
Zhijie Yang ◽  
Courtney R. Funk ◽  
...  
Keyword(s):  
Deletion Mutant ◽  
Lipid A ◽  
Polymyxin B ◽  
Toll Like Receptor ◽  
Inflammatory Signaling ◽  
Toll Like Receptor 4 ◽  
Bioinformatics Analyses ◽  
Monocytic Cells ◽  
Content Type ◽  
High Level

ABSTRACTThe interaction of the immune system withNeisseriacommensals remains poorly understood. We have previously shown that phosphoethanolamine on the lipid A portion of lipooligosaccharide (LOS) plays an important role in Toll-like receptor 4 (TLR4) signaling. For pathogenicNeisseria, phosphoethanolamine is added to lipid A by the phosphoethanolamine transferase specific for lipid A, which is encoded bylptA. Here, we report that Southern hybridizations and bioinformatics analyses of genomic sequences from all eight commensalNeisseriaspecies confirmed thatlptAwas absent in 15 of 17 strains examined but was present inN. lactamica. Mass spectrometry of lipid A and intact LOS revealed the lack of both pyrophosphorylation and phosphoethanolaminylation in lipid A of commensal species lackinglptA. Inflammatory signaling in human THP-1 monocytic cells was much greater with pathogenic than with commensalNeisseriastrains that lackedlptA, and greater sensitivity to polymyxin B was consistent with the absence of phosphoethanolamine. Unlike the other commensals, whole bacteria of twoN. lactamicacommensal strains had low inflammatory potential, whereas their lipid A had high-level pyrophosphorylation and phosphoethanolaminylation and induced high-level inflammatory signaling, supporting previous studies indicating that this species uses mechanisms other than altering lipid A to support commensalism. A meningococcallptAdeletion mutant had reduced inflammatory potential, further illustrating the importance of lipid A pyrophosphorylation and phosphoethanolaminylation in the bioactivity of LOS. Overall, our results indicate that lack of pyrophosphorylation and phosphoethanolaminylation of lipid A contributes to the immune privilege of most commensalNeisseriastrains by reducing the inflammatory potential of LOS.

scholarly journals COVID-19 Patients Upregulate Toll-like Receptor 4-mediated Inflammatory Signaling That Mimics Bacterial Sepsis

2020 ◽  
Vol 35 (38) ◽  
Author(s):  
Kyung Mok Sohn ◽  
Sung-Gwon Lee ◽  
Hyeon Ji Kim ◽  
Shinhyea Cheon ◽  
Hyeongseok Jeong ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Bacterial Sepsis ◽  
Inflammatory Signaling ◽  
Toll Like Receptor 4

scholarly journals Toll-like receptor-4 regulation of hepaticCyp3a11metabolism in a mouse model of LPS-induced CNS inflammation

2005 ◽  
Vol 289 (3) ◽  
pp. G434-G443 ◽  
Author(s):  
Kerry B. Goralski ◽  
Dalya Abdulla ◽  
Christopher J. Sinal ◽  
Andre Arsenault ◽  
Kenneth W. Renton
Keyword(s):  
Mouse Model ◽  
Cns Infection ◽  
Mouse Strains ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cns Inflammation ◽  
Infection And Inflammation ◽  
Cytochrome P 450 ◽  
The Brain ◽  
Expression And Activity

Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 μg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-α and/or IL-1β proteins in the brain. In all mouse strains, LPS produced a 60–70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding the involvement of the hypothalamic-adrenal-pituitary axis. Endotoxin was detectable (1–10 ng/ml) in serum between 15 and 120 min after ICV dosing of 2.5 μg LPS. Peripheral administration of 2.5 μg LPS by intraperitoneal injection produced similar serum endotoxin levels and a similar loss (60%) in Cyp3a11 expression and activity in the liver. The loss of Cyp3a11 in response to centrally or peripherally administered LPS could not be evoked in Toll-like receptor-4 (TLR4)-mutant (C3H/HeJ) mice, indicating that TLR4 signaling pathways are directly involved in the enzyme loss. In summary, we conclude that LPS is transferred from the brain to the circulation in significant quantities in a model of CNS infection or inflammation. Subsequently, LPS that has reached the circulation stimulates a TLR4-dependent mechanism in the periphery, evoking a reduction in Cyp3a11 expression and metabolism in the liver.

Biological role of Toll-like receptor-4 in the brain

2014 ◽  
Vol 268 (1-2) ◽  
pp. 1-12 ◽  
Author(s):  
Teresa Trotta ◽  
Chiara Porro ◽  
Rosa Calvello ◽  
Maria Antonietta Panaro
Keyword(s):  
Biological Role ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
The Brain

scholarly journals Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Antonella Managò ◽  
Valentina Audrito ◽  
Francesca Mazzola ◽  
Leonardo Sorci ◽  
Federica Gaudino ◽  
...  
Keyword(s):  
Endotoxin Tolerance ◽  
Toll Like Receptor ◽  
Biosynthetic Activity ◽  
Toll Like Receptor 4 ◽  
Inflammatory Conditions ◽  
Mouse Macrophages ◽  
Macrophage Colony ◽  
Molecular Patterns

Abstract Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.

scholarly journals Neurosteroid allopregnanolone (3α,5α-THP) inhibits inflammatory signals induced by activated MyD88-dependent toll-like receptors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Irina Balan ◽  
Laure Aurelian ◽  
Riana Schleicher ◽  
Giorgia Boero ◽  
Todd O’Buckley ◽  
...  
Keyword(s):  
Rat Brain ◽  
Toll Like Receptor ◽  
Macrophage Cell ◽  
Toll Like Receptor 4 ◽  
Selective Agonist ◽  
Mouse Macrophages ◽  
Tlr3 Signaling ◽  
The Brain ◽  
Signal Activation ◽  
P Rat

AbstractWe have shown that endogenous neurosteroids, including pregnenolone and 3α,5α-THP inhibit toll-like receptor 4 (TLR4) signal activation in mouse macrophages and the brain of alcohol-preferring (P) rat, which exhibits innate TLR4 signal activation. The current studies were designed to examine whether other activated TLR signals are similarly inhibited by 3α,5α-THP. We report that 3α,5α-THP inhibits selective agonist-mediated activation of TLR2 and TLR7, but not TLR3 signaling in the RAW246.7 macrophage cell line. The TLR4 and TLR7 signals are innately activated in the amygdala and NAc from P rat brains and inhibited by 3α,5α-THP. The TLR2 and TLR3 signals are not activated in P rat brain and they are not affected by 3α,5α-THP. Co-immunoprecipitation studies indicate that 3α,5α-THP inhibits the binding of MyD88 with TLR4 or TLR7 in P rat brain, but the levels of TLR4 co-precipitating with TRIF are not altered by 3α,5α-THP treatment. Collectively, the data indicate that 3α,5α-THP inhibits MyD88- but not TRIF-dependent TLR signal activation and the production of pro-inflammatory mediators through its ability to block TLR-MyD88 binding. These results have applicability to many conditions involving pro-inflammatory TLR activation of cytokines, chemokines, and interferons and support the use of 3α,5α-THP as a therapeutic for inflammatory disease.

Abstract 201: Mice Lacking the Gene for Toll-like Receptor 4 (TLR4) Had an Attenuated ER Stress in the Heart in Response to Ang II Infusion

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Rahul Dange ◽  
Anand R. Nair ◽  
Jorge Vila ◽  
Philip J Ebenezer ◽  
Joseph Francis
Keyword(s):  
Cardiac Hypertrophy ◽  
Er Stress ◽  
Left Ventricular ◽  
Ang Ii ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Rt Pcr ◽  
Toll Like Receptor 4 ◽  
Knock Out ◽  
The Brain

Inflammatory molecule plays an important role in the pathophysiology of hypertension. Recently we showed that TLR4 inhibition in the brain attenuates hypertension. In this study we demonstrate that ANGII induced ER stress in the heart is attenuated in mice lacking the gene for TLR4. In addition, we show that ANGII induced cardiac hypertrophy is blocked by ER stress inhibitor. Method: TLR4 knock-out (KO) mice and wild type (WT) controls were implanted with telemetry probes for mean arterial pressure (MAP) measurements. After collecting baseline MAP and left ventricular function using echocardiography, osmotic minipump containing ANGII (200ng/kg/min) or vehicle (saline) was implanted for 14 days. In another group, C57BL6 mice were injected with ER stress inhibitor 4-PBA (150mg/kg bw) given intraperitoneally with and without ANGII. At the end of the study, mice were sacrificed the LV tissue removed and analyzed for gene of interest using RT-PCR and Western blotting. Results are tabulated. The real-time PCR values are shown as αCT values (18S - the gene of interest). Conclusions: 1) ANGII infusion induces cardiac hypertrophy and ER stress. 2) Mice lacking the gene for TLR4 had attenuated cardiac hypertrophy and ER stress in response to ANGII. 3) ER stress inhibitor protect against ANGII induces cardiac hypertrophy. 4) TLR4 at least in part contributes to ANG II induced cardiac hypertrophy and ER stress.

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