scholarly journals Immunomodulatory Properties of Polysaccharides from the Coral Pseudopterogorgia americana in Macrophages

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3531
Author(s):  
Oleg V. Chernikov ◽  
Hsiao-Wen Chiu ◽  
Lan-Hui Li ◽  
Maxim S. Kokoulin ◽  
Valentina I. Molchanova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mechanistic Study ◽  
Immune Modulators ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Immunomodulatory Properties ◽  
Cox 2 ◽  
Pseudopterogorgia Americana ◽  
Factor Α ◽  
Oxide Synthase

Polysaccharides from marine organisms produce an important regulatory effect on the mammalian immune system. In this study, the immunomodulatory properties of a polysaccharide that was isolated from the coral Pseudopterogorgia americana (PPA) were investigated. PPA increased the expression levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), but not inducible nitric oxide synthase and nitric oxide, in macrophages. A mechanistic study revealed that PPA activated macrophages through the toll-like receptor-4 and induced the generation of reactive oxygen species (ROS), increased the phosphorylation levels of protein kinase C (PKC)-α, PKC-δ and mitogen-activated protein kinases (MAPK), and activated NF-κB. The inhibition of ROS and knockdown of PKC-α reduced PPA-mediated TNF-α and IL-6 expression; however, the knockdown of PKC-δ significantly increased PPA-mediated TNF-α expression. In addition, the inhibition of c-Jun N-terminal kinase-1/2 and NF-κB reduced PPA-mediated TNF-α, IL-6 and COX-2 expression. Furthermore, the inhibition of ROS, MAPK and PKC-α/δ reduced PPA-mediated NF-κB activation, indicating that ROS, MAPK and PKC-α/δ function as upstream signals of NF-κB. Finally, PPA treatment decreased the phagocytosis activity of macrophages and reduced cytokine expression in bacteria-infected macrophages. Taken together, our current findings suggest that PPA can potentially play a role in the development of immune modulators in the future.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 3084-3087 ◽  
Author(s):  
Lars C. Jacobsen ◽  
Kim Theilgaard-Mönch ◽  
Erik I. Christensen ◽  
Niels Borregaard
Keyword(s):  
Nitric Oxide ◽  
Immune Responses ◽  
Tissue Regeneration ◽  
Human Neutrophils ◽  
Arginase 1 ◽  
Tnf Α ◽  
Activated Neutrophils ◽  
Factor Α ◽  
Oxide Synthase ◽  
Extracellular Environment

Abstract Arginase 1 (ARG1) metabolizes arginine, thus reducing the availability of arginine as a substrate for nitric oxide synthase (NOS). The decreased production of nitric oxide (NO) by NOS and the production of ornithine by ARG1 affect immune responses and tissue regeneration at sites of infection, respectively. We here demonstrate that ARG1 is synthesized in myelocytes/metamyelocytes and is stored in gelatinase granules. In accordance with this, activated neutrophils coreleased ARG1 and gelatinase to the extracellular environment on stimulation with phorbol-12-myristate 13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor α (TNF-α). Overall, these findings define ARG1 as a genuine gelatinase granule protein and support a model in which activated neutrophils release ARG1 at sites of infection to modulate immune responses and promote tissue regeneration.

scholarly journals Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 269 ◽  
Author(s):  
Su Cheol Baek ◽  
Dahae Lee ◽  
Mun Seok Jo ◽  
Kwang Ho Lee ◽  
Yong Hoon Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sea Buckthorn ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Cox 2 ◽  
Oxide Synthase

Hippophae rhamnoides L. (Elaeagnaceae; commonly known as “sea buckthorn” and “vitamin tree”), is a spiny deciduous shrub whose fruit is used in foods and traditional medicines. The H. rhamnoides fruit (berry) is rich in vitamin C, with a level exceeding that found in lemons and oranges. H. rhamnoides berries are usually washed and pressed to create pomace and juice. Today, the powder of the aqueous extract of H. rhamnoides berries are sold as a functional food in many countries. As part of our ongoing effort to identify bioactive constituents from natural resources, we aimed to isolate and identify those from the fruits of H. rhamnoides. Phytochemical analysis of the extract of H. rhamnoides fruits led to the isolation and identification of six compounds, namely, a citric acid derivative (1), a phenolic (2), flavonoids (3 and 4), and megastigmane compounds (5 and 6). Treatment with compounds 1–6 did not have any impact on the cell viability of RAW 264.7 mouse macrophages. However, pretreatment with these compounds suppressed lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse macrophages in a concentration-dependent manner. Among the isolated compounds, compound 1 was identified as the most active, with an IC50 of 39.76 ± 0.16 μM. This value was comparable to that of the NG-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor with an IC50 of 28.48 ± 0.05 μM. Western blot analysis demonstrated that compound 1 inhibited the LPS-induced expression of IKKα/β (IκB kinase alpha/beta), I-κBα (inhibitor of kappa B alpha), nuclear factor kappa-B (NF-κB) p65, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) in RAW 264.7 cells. Furthermore, LPS-stimulated cytokine production was detected using a sandwich enzyme-linked immunosorbent assay. Compound 1 decreased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) production in LPS-stimulated RAW 264.7 cells. In summary, the mechanism of action of 1 included the suppression of LPS-induced NO production in RAW 264.7 cells by inhibiting IKKα/β, I-κBα, NF-κB p65, iNOS, and COX-2, and the activities of IL-6 and TNF-α.

scholarly journals Phytosterols Suppress Phagocytosis and Inhibit Inflammatory Mediators via ERK Pathway on LPS-Triggered Inflammatory Responses in RAW264.7 Macrophages and the Correlation with Their Structure

Foods ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 582 ◽  
Author(s):  
Yuan ◽  
Zhang ◽  
Shen ◽  
Jia ◽  
Xie
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Ester Group ◽  
No Production ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase

Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.

Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation

2006 ◽  
Vol 291 (3) ◽  
pp. F567-F577 ◽  
Author(s):  
Li-Mei Chen ◽  
Cindy Wang ◽  
Mengqian Chen ◽  
Matthew R. Marcello ◽  
Julie Chao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
Cytokine Signaling ◽  
Bladder Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with epithelial sodium channel activation and tumor invasion suppression activities. We identified the bladder as an expression site of prostasin. In the mouse, prostasin mRNA expression was detected by reverse transcription and real-time polymerase chain reaction in the bladder, and the prostasin protein was localized by immunohistochemistry in the urothelial cells. In mice injected intraperitoneally with bacterial lipopolysaccharide (LPS), bladder prostasin mRNA expression was downregulated, whereas the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-γ (IFN-γ), TNF-α, IL-1β, and IL-6 was upregulated. Viral promoter-driven expression of the human prostasin homolog in the bladder of transgenic mice attenuated the LPS induction of iNOS but did not abolish the induction. LPS induction of COX-2, TNF-α, IL-1β, and IL-6 expression, however, was not reduced by prostasin transgene expression. Liposome-mediated delivery of prostasin-expressing plasmid into mouse bladder produced similar attenuation effects on LPS-induced iNOS expression, while not affecting COX-2 or cytokine induction. Mice receiving plasmid expressing a catalytic mutant prostasin did not manifest the iNOS induction attenuation phenotype. We propose a proteolytic mechanism for prostasin to intercept cytokine signaling during LPS-induced bladder inflammation.

Anti-Oxidative and Anti-Inflammatory Effects of Lobelia chinensis In Vitro and In Vivo

2015 ◽  
Vol 43 (02) ◽  
pp. 269-287 ◽  
Author(s):  
Kun-Cheng Li ◽  
Yu-Ling Ho ◽  
Guan-Jhong Huang ◽  
Yuan-Shiun Chang
Keyword(s):  
Nitric Oxide ◽  
Folk Medicine ◽  
Ethyl Acetate Fraction ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Factor Α

Lobelia chinensis Lour (LcL) is a popular herb that has been widely used as folk medicine in China for the treatment of fever, lung cancer, and inflammation for hundreds of years. Recently, several studies have shown that the anti-inflammatory properties were correlated with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from the NF-κB pathway. The aim of this study was to evaluate the anti-oxidative and anti-inflammatory activities of L. chinensis. Both suppressive activities on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and the acute rat lung injury model in vivo were studied. The results showed that the methanol extract of LcL and its fractions within the range of 62.5–250 μg/mL did not induce cytotoxicity (p < 0.001). The ethyl acetate fraction of LcL showed better NO inhibition activity than other fractions. On the other hand, the Lc-EA (62.5, 125, 250 mg/kg) pretreated rats showed a decrease in the pro-inflammatory cytokines (TNF-α, IL-β, IL-6) and inhibited iNOS, COX-2 expression through the NF-κB pathway. These results suggested that L. chinensis exhibited an anti-inflammatory effect through the NF-κB pathways.

The role of neuronal NO synthase in the respiratory effects of TNF-α

2021 ◽  
Author(s):  
A.A. Klinnikova ◽  
G.A. Danilova ◽  
N.P. Aleksandrova
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Ventilatory Response ◽  
Neuronal Nitric Oxide Synthase ◽  
Key Words Cytokines ◽  
Respiratory Effects ◽  
Tnf Α ◽  
Before And After ◽  
Factor Α ◽  
Oxide Synthase

It was shown that an increase level of proinflammatory cytokines has a modulating effect on the reflex control of respiration. The aim of this study was to investigate the involvement of neuronal nitric oxide synthase (nNOS) in the mechanisms of the influence of an increased level of Tumor necrosis factor – α (TNF-α) on the hypoxic ventilatory response. To achieve this goal, experiments were carried out on urethane anesthetized rats with intravenous administration of TNF-α before and after pretreatment with 7-nitroindazole specific nNOS inhibitor. The hypoxic ventilation response was assessed by rebreathing with a hypoxic gas mixture before and after administration of TNF-α. We found that TNF-α decreased the ventilatory response to hypoxia. Pretreatment with nNOS inhibitor reduced respiratory effects of TNF-α. Key words: cytokines, TNF-α, hypoxia, chemoreflex, respiration, ventilation, neuronal nitric oxide synthase.

Antithrombin prevents endotoxin-induced hypotension by inhibiting the induction of nitric oxide synthase in rats

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1638-1645 ◽  
Author(s):  
Hirotaka Isobe ◽  
Kenji Okajima ◽  
Mitsuhiro Uchiba ◽  
Naoaki Harada ◽  
Hiroaki Okabe
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Nitric Oxide Synthase ◽  
Messenger Rna ◽  
Inos Mrna ◽  
Therapeutic Effects ◽  
Induced Hypotension ◽  
Tnf Α ◽  
Factor Α ◽  
Oxide Synthase

Antithrombin (AT) prevents Escherichia coli–induced hypotension in animal models of sepsis, and it further reduces the mortality of patients with septic shock. In the present study, we examined whether AT may prevent the endotoxin (ET)-induced hypotension by promoting the endothelial release of prostacyclin (PGI2) in rats. Intravenous administration of AT (250 U/kg) prevented both hypotension and the increases in plasma levels of NO2−/NO3− in rats given ET. Lung expression of messenger RNA (mRNA) for tumor necrosis factor-α (TNF-α) was transiently increased after ET administration, followed by the increases in lung tissue levels of TNF-α. Both the lung activity of the inducible form of nitric oxide synthase (iNOS) and the lung expression of iNOS mRNA in animals administered ET were gradually increased after the TNF-α mRNA expression had peaked. Administration of AT significantly inhibited these increases. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor Trp49-modified AT, which is not capable of promoting the endothelial release of PGI2, showed any effects on these changes induced by ET. Administration of antirat TNF-α antibody produced effects similar to those induced by AT. Indomethacin pretreatment abrogated the effects induced by AT. Iloprost, a stable derivative of PGI2, produced effects similar to those of AT. These findings suggested that AT prevents the ET-induced hypotension by inhibiting the induction of iNOS through inhibiting TNF-α production. These effects of AT could be mediated by the promotion of endothelial release of PGI2 and might at least partly explain the therapeutic effects for septic shock.

scholarly journals Isolation of Novel Sesquiterpeniods and Anti-neuroinflammatory Metabolites from Nardostachys jatamansi

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2367 ◽  
Author(s):  
Chi-Su Yoon ◽  
Dong-Cheol Kim ◽  
Jin-Soo Park ◽  
Kwan-Woo Kim ◽  
Youn-Chul Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
2D Nmr ◽  
Microglial Cells ◽  
No Production ◽  
Nardostachys Jatamansi ◽  
Tnf Α ◽  
Factor Α ◽  
Oxide Synthase ◽  
Bv2 Microglial Cells

Nardostachys jatamansi contains various types of sesquiterpenoids that may play an important role in the potency of plant’s anti-inflammatory effects, depending on their structure. In this study, five new sesquiterpenoids, namely kanshone L (1), kanshone M (2), 7-methoxydesoxo-narchinol (3), kanshone N (4), and nardosdaucanol (5), were isolated along with four known terpenoids (kanshone D (6), nardosinanone G (7), narchinol A (8), and nardoaristolone B (9)) from the rhizomes and roots of Nardostachys jatamansi. Their structures were determined by analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds 3, 4, and 8 were shown to possess dose-dependent inhibitory effects against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2 microglial cells. Furthermore, compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, as well as pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-12 and tumor necrosis factor-α (TNF-α), in LPS-stimulated BV2 microglial cells. Moreover, these compounds were shown to inhibit the activation of the NF-κB signaling pathway in LPS-stimulated BV2 microglial cells by suppressing the phosphorylation of IκB-α and blocking NF-κB translocation. In conclusion, five new and four known sesquiterpenoids were isolated from Nardostachys jatamansi, and compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects in LPS-stimulated BV2 microglial cells through inhibiting of NF-κB signaling pathway.

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