Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages

Lin, Xiaobing; Zhang, Junhan; Fan, Decai; Hou, Ji-Qin; Wang, Hao; Zhu, Lin; Tian, Ruina; An, Xiaofei; Yan, Ming

doi:10.3389/fphar.2021.643188

Cited by 9 publications

(15 citation statements)

References 35 publications

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“…21 LPS, the main component of the outer membrane of Gram-negative bacteria, can stimulate polarization of macrophages to the M1 phenotype, which then secrete a large number of inflammatory factors, such as TNF-α, IL-1β, and iNOS. In the current study, the RT-PCR results indicated that LPS significantly increased the mRNA expression of TNF-α, IL-1β, and iNOS in RAW264.7 cells, which was consistent with literature reports 22–24 and indicated that the macrophage polarization model was successfully constructed. Activation of NLRP3 inflammasomes also plays an important role in the development of atherosclerosis and can mediate M1 macrophage polarization and IL-1β production.…”

Section: Discussionsupporting

confidence: 91%

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages

Wang

Sun

et al. 2022

Journal of Cardiovascular Pharmacology

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:Salidroside has anti-inflammatory and antiatherosclerotic effects, and mitochondrial homeostasis imbalance is closely related to cardiovascular disease. The aim of this study was to investigate the effect of salidroside on mitochondrial homeostasis after macrophage polarization and elucidate its possible mechanism against atherosclerosis. RAW264.7 cells were stimulated with 1 μg·mL−1 Lipopolysaccharide and 50 ng·mL−1 IFN-γ establish M1 polarization and were also pretreated with 400 μM salidroside. The relative expression of proinflammatory genes was detected by RT-PCR whereas that of mitochondrial homeostasis–related proteins and nuclear factor kappa-B (NF-κB) was detected by WB. Levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and mass were measured by chemifluorescence whereas that of NF-κB nuclear translocation was detected by immunofluorescence. Compared with the Mφ group, the M1 group demonstrated increased mRNA expression of interleukin-1β , inductible nitric oxide synthase (iNOS), and tumor necrosis factor-α ; increased protein expression of iNOS, NOD-like receptor protein 3, putative kinase 1 , and NF-κB p65 but decreased protein expression of MFN2, Tom20, and PGC-1α; decreased mitochondrial membrane potential and mass; and increased ROS levels and NF-κB p65 nuclear translocation. Salidroside intervention decreased mRNA expression of interleukin-1β and tumor necrosis factor-α compared with the M1 group but did not affect that of iNOS. Furthermore, salidroside intervention prevented the changes in protein expression, mitochondrial membrane potential and mass, ROS levels, and NF-κB p65 nuclear translocation observed in the M1 group. In summary, salidroside ultimately inhibits M1 macrophage polarization and maintains mitochondrial homeostasis after macrophage polarization by increasing mitochondrial membrane potential, decreasing ROS levels, inhibiting NF-κB activation, and in turn regulating the expression of proinflammatory factors and mitochondrial homeostasis–associated proteins.

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Section: Discussionsupporting

confidence: 91%

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages

Wang

Sun

et al. 2022

Journal of Cardiovascular Pharmacology

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“…LPS is known to activate TLR4 receptor for the production of NO and immune cytokines via activation of IKKα/β, which was phosphorylated to release NF-κB from the cytoplasmic NF-κB/ IKK complex to undergo nuclear translocation and enter the nucleus to promote the transcription of inflammatory cytokines. 25,26 As shown in Figure 8, compound 7 significantly increased the phosphorylation of IKKα and IKKβ and suppressed the expression of NF-κB in a concentrationdependent manner. The thermal stabilization of TLR4 upon binding with 7 was shown in Figure 9A,B.…”

Section: ■ Results and Discussionmentioning

confidence: 92%

Pyranochromones with Anti-Inflammatory Activities in Arthritis from Calophyllum membranaceum

Shen

et al. 2022

J. Nat. Prod.

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Eleven new pyranochromones, calomembranone A−K (1−11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14−19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure−activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC 50 = 0.92 μM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-tolymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.

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“…In the present study, we constructed a mouse model of AP by administrating cerulein plus LPS, and we questioned whether LPS treatment caused the difference. LPS is an agonist of Toll-like receptor 4 (TLR4) and can activate its downstream NF-κB and MAPK pathways [ 38 , 39 ]; it can also directly activate caspase11 independently of TLR4 [ 40 ]. Therefore, we detected the activation of the NF-κB, MAPK and Caspase11 pathways in WT, Mlkl -/- , and Ripk3 -/- mice with AP and their controls.…”

Section: Resultsmentioning

confidence: 99%

MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10

Pan

Wang

et al. 2023

Cell Death Dis

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Acute pancreatitis (AP) is a disease characterized by local and systemic inflammation with an increasing incidence worldwide. Receptor-interacting serine/threonine protein kinase 3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), and innate immune cell macrophages have been reported to be involved in the pathogenesis of AP. However, the mechanisms by which RIPK3 and MLKL regulate pancreatic injury, as well as the interactions between injured pancreatic acinar cells and infiltrating macrophages in AP, remain poorly defined. In the present study, experimental pancreatitis was induced in C57BL/6J, Ripk3-/- and Mlkl-/- mice by cerulein plus lipopolysaccharide in vivo, and primary pancreatic acinar cells were also isolated to uncover cellular mechanisms during cerulein stimulation in vitro. The results showed that MLKL and its phosphorylated protein p-MLKL were upregulated in the pancreas of the mouse AP model and cerulein-treated pancreatic acinar cells, independent of its canonical upstream molecule Ripk3, and appeared to function in a cell death-independent manner. Knockout of Mlkl attenuated AP in mice by reducing the polarization of pancreatic macrophages toward the M1 phenotype, and this protective effect was partly achieved by reducing the secretion of CXCL10 from pancreatic acinar cells, whereas knockout of Ripk3 did not. In vitro neutralization of CXCL10 impaired the pro-M1 ability of the conditioned medium of cerulein-treated pancreatic acinar cells, whereas in vivo neutralization of CXCL10 reduced the polarization of pancreatic macrophages toward M1 and the severity of AP in mice. These findings suggested that targeting the MLKL-CXCL10-macrophage axis might be a promising strategy for the treatment of AP.

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Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages

Cited by 9 publications

References 35 publications

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages

Pyranochromones with Anti-Inflammatory Activities in Arthritis from Calophyllum membranaceum

MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10

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