scholarly journals Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Miriam Maraslioglu ◽  
Elsie Oppermann ◽  
Carolin Blattner ◽  
Roxane Weber ◽  
Dirk Henrich ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Intracellular Signalling ◽  
Chronic Ethanol ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Ethanol Feeding

Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding onin vivoactivation of NF-κB in NF-κBEGFPreporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-αand activation of NF-κB after chronic ethanol feeding followed byin vitrostimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1βrelease from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-αlevels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-αproduction and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-αstimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.

scholarly journals Anti-Inflammatory Effects ofSiegesbeckia orientalisEthanol Extract inIn VitroandIn VivoModels

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yong-Han Hong ◽  
Li-Wen Weng ◽  
Chi-Chang Chang ◽  
Hsia-Fen Hsu ◽  
Chao-Ping Wang ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Animal Experiments ◽  
Ethanol Extract ◽  
Raw264.7 Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Anti Inflammatory

This study aims to investigate the anti-inflammatory responses and mechanisms ofSiegesbeckia orientalisethanol extract (SOE). In cell culture experiments, RAW264.7 cells were pretreated with SOE and stimulated with lipopolysaccharide (LPS) for inflammatory mediators assay. In animal experiments, mice were tube-fed with SOE for 1 week, and s.c. injected withλ-carrageenan or i.p. injected with LPS to simulate inflammation. The degree of paw edema was assessed, and cytokine profile in sera and mouse survival were recorded. Data showed that SOE significantly reduced NO, IL-6, and TNF-α production in LPS-stimulated RAW264.7 cells.In vivostudies demonstrated that mice supplemented with 32 mg SOE/kg BW/day significantly lowered sera IL-6 level and resulted a higher survival rate compared to the control group (P=0.019). Furthermore, SOE inhibited LPS-induced NF-κB activation by blocking the degradation of IκB-α. The SOE also reduced significantly the phosphorylation of ERK1/2, p38, and JNK in a dose-dependent manner. In summary, thein vitroandin vivoevidence indicate that SOE can attenuate acute inflammation by inhibiting inflammatory mediators via suppression of MAPKs- and NF-κB-dependent pathways.

scholarly journals Antitumor Efficacy of the Herbal Recipe Benja Amarit against Highly Invasive Cholangiocarcinoma by Inducing Apoptosis both In Vitro and In Vivo

2020 ◽  
Vol 21 (16) ◽  
pp. 5669
Author(s):  
Rittibet Yapasert ◽  
Nirush Lertprasertsuk ◽  
Subhawat Subhawa ◽  
Juthathip Poofery ◽  
Bungorn Sripanidkulchai ◽  
...  
Keyword(s):  
Xenograft Model ◽  
Nuclear Factor Κb ◽  
Mechanisms Of Action ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
The World ◽  
Dose Dependent ◽  
Growth Inhibiting

Thailand is the country with highest incidence and prevalence of cholangiocarcinoma (CCA) in the world. Due to the frequently late diagnosis that is associated with this disease, most CCA patients are prescribed chemotherapy as a form of treatment. However, CCA is able to resist the presently available chemotherapy, so to the prognosis of this disease is still very poor. In this study, we investigated the anticancer potential of a Thai herbal recipe, Benja Amarit (BJA) against CCA and the relevant mechanisms of action that are involved. We found that BJA inhibited CCA cell viability in a dose-dependent manner, especially in highly invasive KKU-213 cells. The extract induced mitochondrial- and caspase-dependent apoptosis in CCA cells by regulating the nuclear factor-κB (NF-κB) signaling pathway. BJA also triggered autophagy in CCA cells. Nonetheless, the inhibition of autophagy enhanced BJA-induced CCA cell death via apoptosis. An in vivo xenograft model revealed the growth-inhibiting and death-inducing effects of BJA against CCA by targeting apoptosis. However, general toxicity to blood cells, kidneys and the liver, as well as changes in body weight, did not appear. Our findings suggest that the herbal recipe BJA might be used as a potentially new and effective treatment for cholangiocarcinoma patients.

scholarly journals Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment

2019 ◽  
Vol 8 (12) ◽  
pp. 2091 ◽  
Author(s):  
Stuart B. Goodman ◽  
Jiri Gallo
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Periprosthetic Osteolysis ◽  
Bone Implant ◽  
Joint Replacements ◽  
In Vivo Experiments ◽  
Mechanical Factors

Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone–implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are evidence based. To date, the most successful and effective approach to preventing PPOL is usage of wear-resistant bearing couples in combination with advanced implant designs, reducing the load of metallic and polymer particles. These innovations have significantly decreased the revision rate due to AL and PPOL in the last decade.

In Vitro and in Vivo Nuclear Factor-κB Inhibitory Effects of the Cell-Penetrating Penetratin Peptide

2006 ◽  
Vol 69 (6) ◽  
pp. 2027-2036 ◽  
Author(s):  
Tamás Letoha ◽  
Erzsébet Kusz ◽  
Gábor Pápai ◽  
Annamária Szabolcs ◽  
József Kaszaki ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Inhibitory Effects ◽  
Cell Penetrating

Fucoidans from Cucumaria frondosa ameliorates renal interstitial fibrosis via inhibition of PI3K/Akt/NF-κB signaling pathway

2022 ◽  
Author(s):  
Zhuo-yue Song ◽  
Mengru Zhu ◽  
Jun Wu ◽  
Tian Yu ◽  
Yao Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Protein Kinase B ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Renal Interstitial Fibrosis ◽  
Cucumaria Frondosa

The effects of Cucumaria frondosa polysaccharides (CFP) on renal interstitial fibrosis via regulating phosphatidylinositol-3-hydroxykinase/protein kinase-B/Nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. A...

A dual-action peptide-containing hydrogel targets wound infection and inflammation

2020 ◽  
Vol 12 (524) ◽  
pp. eaax6601 ◽  
Author(s):  
Manoj Puthia ◽  
Marta Butrym ◽  
Jitka Petrlova ◽  
Ann-Charlotte Strömdahl ◽  
Madelene Å. Andersson ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Nuclear Factor Κb ◽  
Reporter Mice ◽  
Dual Action ◽  
Infection And Inflammation ◽  
Molecular Patterns

There is a clinical need for improved wound treatments that prevent both infection and excessive inflammation. TCP-25, a thrombin-derived peptide, is antibacterial and scavenges pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide, thereby preventing CD14 interaction and Toll-like receptor dimerization, leading to reduced downstream immune activation. Here, we describe the development of a hydrogel formulation that was functionalized with TCP-25 to target bacteria and associated PAMP-induced inflammation. In vitro studies determined the polymer prerequisites for such TCP-25–mediated dual action, favoring the use of noncharged hydrophilic hydrogels, which enabled peptide conformational changes and LPS binding. The TCP-25–functionalized hydrogels killed Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria in vitro, as well as in experimental mouse models of subcutaneous infection. The TCP-25 hydrogel also mediated reduction of LPS-induced local inflammatory responses, as demonstrated by analysis of local cytokine production and in vivo bioimaging using nuclear factor κB (NF-κB) reporter mice. In porcine partial thickness wound models, TCP-25 prevented infection with S. aureus and reduced concentrations of proinflammatory cytokines. Proteolytic fragmentation of TCP-25 in vitro yielded a series of bioactive TCP fragments that were identical or similar to those present in wounds in vivo. Together, the results demonstrate the therapeutic potential of TCP-25 hydrogel, a wound treatment based on the body’s peptide defense, for prevention of both bacterial infection and the accompanying inflammation.

Pentoxifylline inhibits FMLP-induced macromolecular leakage

1995 ◽  
Vol 269 (1) ◽  
pp. H239-H245
Author(s):  
K. Nakagawa ◽  
F. N. Miller ◽  
A. W. Knott ◽  
M. J. Edwards
Keyword(s):  
Inflammatory Responses ◽  
Fluorescein Isothiocyanate ◽  
Histamine Receptor ◽  
Intracellular Camp ◽  
Dependent Manner ◽  
Cyclic Monophosphate ◽  
Endogenous Histamine ◽  
Camp Analogue

The acute inflammatory responses to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the effects of pentoxifylline (PTXF) on the responses in vivo were studied. We used intravital microscopy with rat cremaster muscle preparation to determine inflammatory responses of microcirculation. Macromolecular leakage from postcapillary venules was evaluated by quantifying the extravasation of fluorescein isothiocyanate conjugated to bovine serum albumin. FMLP induced a rapid increase in macromolecular leakage, an increase in leukocyte-endothelium adhesion, and a decrease in blood flow in the microcirculation. PTXF inhibited FMLP-induced responses in a dose-dependent manner but failed to block the histamine-dependent leakage induced by compound 48/80. In addition, diphenhydramine, a histamine-receptor blocker, did not affect the macromolecular leakage induced by FMLP. The cell-permeable adenosine 3',5'-cyclic monophosphate (cAMP) analogue N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate mimicked PTXF's effects on the microcirculation and also inhibited FMLP-induced macromolecular leakage. PTXF is known to inhibit phosphodiesterase and increase intracellular cAMP, which modulates functions of endothelial cells, smooth muscle cells, and neutrophils in vitro. Our findings suggest that FMLP induces acute inflammatory responses through activation of neutrophils, independent of endogenous histamine release, and that PTXF inhibits these responses through elevated intracellular cAMP.

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