scholarly journals Hirsutanol A Attenuates Lipopolysaccharide-Mediated Matrix Metalloproteinase 9 Expression and Cytokines Production and Improves Endotoxemia-Induced Acute Sickness Behavior and Acute Lung Injury

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 360 ◽  
Author(s):  
Jan ◽  
Yang ◽  
Wang ◽  
Lin ◽  
Yen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inflammatory Diseases ◽  
Sickness Behavior ◽  
Inflammatory Cells ◽  
Marine Fungus ◽  
Motor Deficits ◽  
Interstitial Tissue ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Acute Sickness

Activated human monocytes/macrophages, which increase the levels of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines, are the essential mechanisms for the progression of sepsis. In the present study, we determined the functions and mechanisms of hirsutanolA (HA), which is isolated from the red alga-derived marine fungus Chondrostereum sp. NTOU4196, on the production of pro-inflammatory mediators produced from lipopolysaccharide (LPS)-treated THP-1 cells. Our results showed that HA suppressed LPS-triggered MMP-9-mediated gelatinolysis and expression of protein and mRNA in a concentration-dependent manner without effects on TIMP-1 activity. Also, HA significantly attenuated the levels of TNF-α, IL-6, and IL-1β from LPS-treated THP-1 cells. Moreover, HA significantly inhibited LPS-mediated STAT3 (Tyr705) phosphorylation, IκBα degradation and ERK1/2 activation in THP-1 cells. In an LPS-induced endotoxemia mouse model, studies indicated that HA pretreatment improved endotoxemia-induced acute sickness behavior, including acute motor deficits and anxiety-like behavior. HA also attenuated LPS-induced phospho-STAT3 and pro-MMP-9 activity in the hippocampus. Notably, HA reduced pathologic lung injury features, including interstitial tissue edema, infiltration of inflammatory cells and alveolar collapse. Likewise, HA suppressed the induction of phospho-STAT3 and pro-MMP-9 in lung tissues. In conclusion, our results provide pharmacological evidence that HA could be a useful agent for treating inflammatory diseases, including sepsis.

scholarly journals Effects of shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) on prostaglandin E2 production in lipopolysaccharide-treated mouse macrophage RAW264.7 cells

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7725 ◽  
Author(s):  
Toshiaki Ara ◽  
Masanori Koide ◽  
Hiroyuki Kitamura ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Diseases ◽  
Treated Mouse ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Mouse Macrophage ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Concentration Dependent Manner ◽  
Inflammatory Drugs

We previously reported that shokyo and kankyo, which are water-extracted fractions of ginger, reduced LPS-induced PGE2 production in human gingival fibroblasts. In this study, we examined the effects of these herbs on LPS-treated mouse macrophage RAW264.7 cells. Both shokyo and kankyo reduced LPS-induced PGE2 production in a concentration-dependent manner. Shokyo and kankyo did not inhibit cyclooxygenase (COX) activity, nor did they alter the expression of molecules in the arachidonic acid cascade. In addition, these herbs did not alter NF-κB p65 translocation into nucleus, or phosphorylation of p65 or ERK. These results suggest that shokyo and kankyo inhibit cPLA2 activity. Although 6-shogaol produced similar results to those of shokyo and kankyo, the concentration of 6-shogaol required for the reduction of PGE2 production were higher than those of 6-shogaol in shokyo and kankyo. Therefore, several gingerols and shogaols other than 6-shogaol may play a role in the reduction of LPS-induced PGE2 production. Thus, 6-shogaol, and other gingerols and shogaols inhibit cPLA2 activity and reduce LPS-induced PGE2 production via a different mechanism from traditional anti-inflammatory drugs. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for inflammatory diseases.

Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1911-1917 ◽  
Author(s):  
Gita T. Kampen ◽  
Susan Stafford ◽  
Tetsuya Adachi ◽  
Tan Jinquan ◽  
Sha Quan ◽  
...  
Keyword(s):  
Map Kinases ◽  
Inflammatory Diseases ◽  
Eosinophil Cationic Protein ◽  
Dependent Manner ◽  
Cationic Protein ◽  
Concentration Dependent Manner ◽  
P38 Inhibitor ◽  
Mitogen Activated Protein ◽  
Integral Role ◽  
Functional Relevance

Abstract Eotaxin and other CC chemokines acting via CC chemokine receptor-3 (CCR3) are believed to play an integral role in the development of eosinophilic inflammation in asthma and allergic inflammatory diseases. However, little is known about the intracellular events following agonist binding to CCR3 and the relationship of these events to the functional response of the cell. The objectives of this study were to investigate CCR3-mediated activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase-2 (ERK2), p38, and c-jun N-terminal kinase (JNK) in eosinophils and to assess the requirement for MAP kinases in eotaxin-induced eosinophil cationic protein (ECP) release and chemotaxis. MAP kinase activation was studied in eotaxin-stimulated eosinophils (more than 97% purity) by Western blotting and immune-complex kinase assays. ECP release was measured by radioimmunoassay. Chemotaxis was assessed using Boyden microchambers. Eotaxin (10−11 to 10−7 mol/L) induced concentration-dependent phosphorylation of ERK2 and p38. Phosphorylation was detectable after 30 seconds, peaked at about 1 minute, and returned to baseline after 2 to 5 minutes. Phosphorylation of JNK above baseline could not be detected. The kinase activity of ERK2 and p38 paralleled phosphorylation. PD980 59, an inhibitor of the ERK2-activating enzyme MEK (MAP ERK kinase), blocked phosphorylation of ERK2 in a concentration-dependent manner. The functional relevance of ERK2 and p38 was studied using PD98 059 and the p38 inhibitor SB202 190. PD98 059 and SB202 190 both caused inhibition of eotaxin-induced ECP release and chemotaxis. We conclude that eotaxin induces a rapid concentration-dependent activation of ERK2 and p38 in eosinophils and that the activation of these MAP kinases is required for eotaxin-stimulated degranulation and directed locomotion.

scholarly journals Human macrophages convert l-tryptophan into the neurotoxin quinolinic acid

1992 ◽  
Vol 283 (3) ◽  
pp. 633-635 ◽  
Author(s):  
M P Heyes ◽  
K Saito ◽  
S P Markey
Keyword(s):  
Interferon Gamma ◽  
Quinolinic Acid ◽  
Receptor Agonist ◽  
Chemical Ionization ◽  
Inflammatory Diseases ◽  
Human Peripheral Blood ◽  
Inflammatory Cells ◽  
Ionization Mass ◽  
Dependent Manner ◽  
Aspartate Receptor

Substantial increases in the concentrations of the excitotoxin and N-methyl-D-aspartate-receptor agonist quinolinic acid (QUIN) occur in human patients and non-human primates with inflammatory diseases. Such increases were postulated to be secondary to induction of indoleamine 2,3-dioxygenase in inflammatory cells, particularly macrophages, by interferon-gamma. To test this hypothesis, human peripheral-blood macrophages were incubated with L-[13C6]tryptophan in the absence or presence of interferon-gamma. [13C6]QUIN was quantified by gas chromatography and electron-capture negative-chemical-ionization mass spectrometry. [13C6]QUIN was detected in the incubation medium of both unstimulated and stimulated cultures. Exposure to interferon-gamma substantially increased the accumulation of [13C6]QUIN in a dose- and time-dependent manner. The QUIN concentrations achieved exceeded those reported in both cerebrospinal fluid and blood of patients and of non-human primates with inflammatory diseases. Macrophages stimulated with interferon-gamma may be an important source of accelerated L-tryptophan conversion into QUIN in inflammatory diseases.

scholarly journals Monoterpenoids from the Fruits of Amomum tsao-ko Have Inhibitory Effects on Nitric Oxide Production

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 257
Author(s):  
Seong Su Hong ◽  
Ji Eun Lee ◽  
Yeon Woo Jung ◽  
Ju-Hyoung Park ◽  
Jung A. Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Dependent Manner ◽  
Interleukin 1 Beta ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
First Time

In our search for novel plant-derived inhibitors of nitric oxide (NO) with potential for treating inflammatory diseases, the phytochemicals of Amomum tsao-ko fruits were investigated, leading to the isolation of one bicyclic nonane (1), three menthene skeleton monoterpenoids (2–4), and two acyclic monoterpenoids (5 and 6). Their structures were identified using one- and two-dimensional nuclear magnetic resonance spectroscopy, and mass spectrometry. To the best of our knowledge, compounds 2–5 were obtained from the genus Amomum for the first time. All isolates were tested for their ability to inhibit lipopolysaccharide-stimulated NO overproduction in RAW264.7 cells. Compound 4 was found to inhibit NO production. Western blotting analysis indicated that active compound 4 can regulate inducible NO synthase expression. In addition, lipopolysaccharide-induced interleukin 1 beta and interleukin-6 overproduction was reduced in a concentration-dependent manner.

scholarly journals Royal Jelly Attenuates LPS-Induced Inflammation in BV-2 Microglial Cells through Modulating NF-κB and p38/JNK Signaling Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Meng-Meng You ◽  
Yi-Fan Chen ◽  
Yong-Ming Pan ◽  
Yi-Chen Liu ◽  
Jue Tu ◽  
...  
Keyword(s):  
Functional Food ◽  
Molecular Mechanisms ◽  
Royal Jelly ◽  
Inflammatory Diseases ◽  
Microglial Cells ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anti Inflammatory

Royal jelly (RJ), a hive product with versatile pharmacological activities, has been used as a traditional functional food to prevent or treat inflammatory diseases. However, little is known about the anti-inflammatory effect of RJ in microglial cells. The aim of this study is to assess the anti-inflammatory effects of RJ in lipopolysaccharide- (LPS-) induced murine immortalized BV-2 cells and to explore the underlying molecular mechanisms. Our results showed that in LPS-stimulated BV-2 cells, RJ significantly inhibited iNOS and COX-2 expression at mRNA and protein levels. The mRNA expression of IL-6, IL-1β, and TNF-α was also downregulated by RJ in a concentration-dependent manner. Additionally, RJ protected BV-2 cells against oxidative stress by upregulating heme oxygenase-1 (HO-1) expression and by reducing reactive oxygen species (ROS) and nitric oxide (NO) production. Mechanistically, we found that RJ could alleviate inflammatory response in microglia by suppressing the phosphorylation of IκBα, p38, and JNK and by inhibiting the nucleus translocation of NF-κB p65. These findings suggest that RJ might be a promising functional food to delay inflammatory progress by influencing the microglia function.

scholarly journals Luteolin Suppresses Inflammatory Mediator Expression by Blocking the Akt/NFκB Pathway in Acute Lung Injury Induced by Lipopolysaccharide in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Ching Li ◽  
Chung-Hsin Yeh ◽  
Ming-Ling Yang ◽  
Yu-Hsiang Kuan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Specific Treatment ◽  
Severe Illness ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Protection Mechanism ◽  
Tissue Edema ◽  
Nfκb Pathway

Acute lung injury (ALI), instilled by lipopolysaccharide (LPS), is a severe illness with excessive mortality and has no specific treatment strategy. Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants. Pretreatment with luteolin inhibited LPS-induced histological changes of ALI and lung tissue edema. In addition, LPS-induced inflammatory responses, including increased vascular permeability, tumor necrosis factor (TNF)-αand interleukin (IL)-6 production, and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), were also reduced by luteolin in a concentration-dependent manner. Furthermore, luteolin suppressed activation of NFκB and its upstream molecular factor, Akt. These results suggest that the protection mechanism of luteolin is by inhibition of NFκB activation possibly via Akt.

scholarly journals Neolitsea Sericea Essential Oil Attenuates LPS-induced Inflammation in RAW 264.7 Macrophages by Suppressing NF-κB and MAPK Activation

2010 ◽  
Vol 5 (8) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Weon-Jong Yoon ◽  
Ji-Young Moon ◽  
Ji-Yong Kang ◽  
Gi-Ok Kim ◽  
Nam Ho Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Essential Oil ◽  
Inflammatory Diseases ◽  
Chemical Constituents ◽  
Nuclear Factor Κb ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Raw 264.7 Macrophages

The chemical composition and antiinflammatory activities of hydrodistilled essential oil from Neolitsea sericea leaves (NSE) have been investigated for the first time. The chemical constituents of NSE were analysed by GC-MS and found to include sericenine (32.3%), sabinene (21.0%), trans-β-ocimene (13.3%), β-caryophyllene (4.8%), and 4-terpineol (4.2%). The effects of NSE on nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. Pro-inflammatory cytokine and mediator tests indicated that NSE has excellent dose-dependent inhibitory activities. To further examine the mechanism responsible for the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression by NSE, we examined the effect of NSE on nuclear factor-κB (NF-κB) activation and the phosphorylation of mitogen-activated protein kinases (MAPK). NSE inhibited NF-κB activation by LPS, and this was associated with the abrogation of IκB-α phosphorylation and subsequent decreases in nuclear p50 and p65 protein levels. Further, the phosphorylation of p38, ERK and JNK was suppressed by NSE in a concentration-dependent manner. These results suggest that NSE exerts antiinflammatory effects in LPS-stimulated RAW 264.7 macrophages by inhibition of NF-κB activation and MAPK phosphorylation, and, therefore, may be useful for treatment of inflammatory diseases.

Two indole-2-carboxamide derivatives attenuate lipopolysaccharide-induced acute lung injury by inhibiting inflammatory response

2018 ◽  
Vol 96 (12) ◽  
pp. 1261-1267
Author(s):  
Wei Dai ◽  
Xiangting Ge ◽  
Tingting Xu ◽  
Chun Lu ◽  
Wangfeng Zhou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Genes Expression ◽  
Tnf Α ◽  
Induced Changes

Acute lung injury (ALI) is the leading cause of mortality in the intensive care unit. Currently, there is no effective pharmacological treatment for ALI. In our previous study, we reported that Lg25 and Lg26, two indole-2-carboxamide derivatives, inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokines in vitro and attenuated LPS-induced sepsis in vivo. In the present study, we confirmed data from previous studies that LPS significantly induced pulmonary edema and pathological changes in lung tissue, increased protein concentration and number of inflammatory cells in bronchoalveolar lavage fluids (BALF), and increased inflammatory cytokine TNF-α expression in serum and BALF, pro-inflammatory genes expression, and macrophages infiltration in lung tissue. However, pretreatment with Lg25 and Lg26 significantly attenuated the LPS-induced changes in mice. Taken together, these data indicate that the newly discovered indole-2-carboxamide derivatives could be particularly useful in the treatment of inflammatory diseases such as ALI.

Cranberry Proanthocyanidins Inhibit MMP Production and Activity

2009 ◽  
Vol 88 (7) ◽  
pp. 627-632 ◽  
Author(s):  
V.D. La ◽  
A.B. Howell ◽  
D. Grenier
Keyword(s):  
Catalytic Activity ◽  
Nuclear Factor Kappa B ◽  
Human Monocyte ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Periodontal Tissue ◽  
Tissue Destruction ◽  
Concentration Dependent Manner ◽  
Novel Host

Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in periodontal tissue destruction. Our aim was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on: (i) the production of various MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), and (ii) the catalytic activity of recombinant MMP-1 and MMP-9. The effects of AC-PACs on the expression of 5 protein kinases and the activity of nuclear factor-kappa B (NF-κB) p65 in macrophages stimulated with LPS were also monitored. Our results indicated that AC-PACs inhibited the production of MMPs in a concentration-dependent manner. Furthermore, the catalytic activity of MMP-1 and MMP-9 was also inhibited. The inhibition of MMP production was associated with reduced phosphorylation of key intracellular kinases and the inhibition of NF-κB p65 activity. AC-PACs thus show potential for the development of novel host-modulating strategies to inhibit MMP-mediated tissue destruction during periodontitis.

scholarly journals Evaluation of the Effects of Some Brazilian Medicinal Plants on the Production of TNF-αand CCL2 by THP-1 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Grasielle S. Gusman ◽  
Priscilla R. V. Campana ◽  
Luciano C. Castro ◽  
Rachel O. Castilho ◽  
Mauro M. Teixeira ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Dependent Manner ◽  
Scavenging Activity ◽  
Monocytic Leukemia ◽  
Concentration Dependent Manner ◽  
Highly Active

Several plant species are traditionally used in Brazil to treat various inflammatory diseases. Tumor necrosis factor- (TNF-)αand chemokine (C-C motif) ligand 2 (CCL2) are key inflammatory mediators in diseases like rheumatoid arthritis and atherosclerosis, respectively; nevertheless, only a few extracts have been assayed against these targets. We herein report the effect of 19 plant extracts on TNF-αand CCL2 release by lipopolysaccharide- (LPS-) stimulated THP-1 cells, a human monocytic leukemia cell line, along with their radical scavenging activity on DPPH. The extracts ofCaryocar brasiliense,Casearia sylvestris,Coccoloba cereifera, andTerminalia glabrescensinhibited TNF-αproduction in a concentration-dependent manner. Fractionation of these extracts potentiated the anti-TNF-αeffect, which was shown to concentrate in polar fractions, mainly composed by polyphenols. Significant CCL2 inhibition was elicited byLippia sidoidesandTerminalia glabrescensextracts, whose fractionation resulted in highly active low polar fractions. All assayed extracts showed strong radical scavenging activity, but antioxidant activity did not correlate with inhibition of TNF-αor CCL2 production. Our results allowed identifying extracts with selective capacity to block cytokine production; therefore, further purification of these extracts may yield molecules that could be useful in the treatment of chronic inflammatory diseases.

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