Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor‐<i>α</i> by inhibiting nuclear factor‐<i>κ</i>B activation

Posadas, Inmaculada; Rosa, Salvatore De; Terencio, María Carmen; Payá, Miguel; Alcaraz, Marı́a José

doi:10.1038/sj.bjp.0705189

Cited by 36 publications

(22 citation statements)

References 35 publications

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“…These cells contained levels of COX-2 protein that were much higher than those observed in RPMs that had not been exposed to LPS or zymosan (in which COX-2 was nearly undetectable). These results suggest that zymosan induced COX-2 expression, consistent with prior reports (41)(42)(43)(44)(45), and led to the hypothesis that zymosan-induced COX-2 may be responsible for the PG-G synthesis in these cells.…”

Section: Synthesis Of Pg-gs From Endogenous Substrate By Rpms During supporting

confidence: 91%

Glycerylprostaglandin Synthesis by Resident Peritoneal Macrophages in Response to a Zymosan Stimulus

Rouzer

Marnett

2005

Journal of Biological Chemistry

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Cyclooxygenase (COX)-2 oxygenates arachidonic acid (AA) and 2-arachidonylglycerol (2-AG) to endoperoxides, which are subsequently transformed to prostaglandins (PGs) and glycerylprostaglandins (PG-Gs). PG-G formation has not been demonstrated in intact cells treated with a physiological agonist. Resident peritoneal macrophages, which express COX-1, were pretreated with lipopolysaccharide to induce COX-2. Addition of zymosan caused release of 2-AG and production of the glyceryl esters of PGE 2 and PGI 2 over 60 min. The total quantity of PG-Gs (16 ؎ 6 pmol/10 7 cells) was much lower than that of the corresponding PGs produced from AA (21,000 ؎ 7,000 pmol/10 7 cells). The differences in PG-G and PG production were partially explained by differences in the amounts of 2-AG and AA released in response to zymosan. The selective COX-2 inhibitor, SC236, reduced PG-G and PG production by 49 and 17%, respectively, indicating a significant role for COX-1 in PG-G and especially PG synthesis. Time course studies indicated that COX-2-dependent oxygenation rapidly declined 20 min after zymosan addition. When exogenous 2-AG was added to macrophages, a substantial portion was hydrolyzed to AA and converted to PGs; 1 M 2-AG yielded 820 ؎ 200 pmol of PGs/10 7 cells and 78 ؎ 41 pmol of PG-Gs/10 7 cells. SC236 reduced PG-G and PG production from exogenous 2-AG by 88 and 76%, respectively, indicating a more significant role for COX-2 in the utilization of exogenous substrate. In conclusion, lipopolysaccharide-pretreated macrophages produce PG-Gs from endogenous 2-AG during zymosan phagocytosis, but PG-G formation is limited by substrate hydrolysis and inactivation of COX-2.Cyclooxygenase (COX 1 ; prostaglandin G/H synthase) catalyzes the first two steps in the conversion of arachidonic acid (AA) to prostaglandins (PG), prostacyclin, and thromboxane (1-4). The product of the COX reaction is the endoperoxide, PGH 2 , which is then further metabolized to the terminal PGs through the action of various synthase enzymes. Two isoforms of COX have been identified and characterized (5). The isoforms differ considerably with regard to transcriptional regulation in that COX-1 is usually expressed constitutively, whereas COX-2 is induced in response to a variety of inflammatory and proliferative stimuli, including cytokines, growth factors, and tumor promoters. As a consequence of these varied expression patterns, COX-1 is believed to be primarily responsible for "housekeeping" functions such as gastric cytoprotection and regulation of platelet aggregation. In contrast, COX-2 is thought to be involved in the inflammatory response, pyrexia, and in the regulation of cellular proliferation (6 -11). However, recent work has indicated that these distinct roles are probably oversimplified, leaving an ongoing question as to the exact physiological functions of each isoform (12).Despite their differences in transcriptional regulation, COX-1 and COX-2 share 60% sequence identity, with nearly superimposable three-dimensional structures and highly similar ...

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Section: Synthesis Of Pg-gs From Endogenous Substrate By Rpms During supporting

confidence: 91%

Glycerylprostaglandin Synthesis by Resident Peritoneal Macrophages in Response to a Zymosan Stimulus

Rouzer

Marnett

2005

Journal of Biological Chemistry

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“…Peritoneal macrophages were obtained as previously described (27). Female C57BL/6j mice (Janvier) weighing 25-30 g were used to obtain highly purified peritoneal macrophages.…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear and cytosolic extracts from macrophages were prepared as previously described (27). Cells seeded in six-well culture plates treated with vehicle (1‰ DMSO) or 100 ng/mL LPS in the presence or absence of different concentrations of phosphorus dendrimers or 5 μM MG-132 for different times.…”

Section: Methodsmentioning

confidence: 99%

“…Air pouches were produced as previously described (27) by s.c. injection of 10-mL sterile air into the back of Female C57BL/6j mice (Janvier) weighing 25-30 g. Three days later 5-mL sterile air was injected into the same cavity. Six days after the initial air injection, animals were divided in six experimental groups (each one comprising four animals) that received the following treatments: (i) vehicle, sterile saline (1 mL) containing 1 0 / 00 DMSO in the air pouch; (ii) G3bis, 10 mg/kg i.v; (iii) G4bis, 10 mg/kg i.v; (iv) Zymosan, 1% wt/vol zymosan in saline in the air pouch; (v) Zymosan+G3 bis, 1% wt/vol zymosan in saline in the air pouch + G3bis, 10 mg/kg i.v; (vi) Zymosan+G4 bis, 1% wt/vol zymosan in saline in the air pouch + G4bis, 10 mg/kg i.v (Fig.…”

Section: Methodsmentioning

confidence: 99%

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Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Posadas

Romero-Castillo

Brahmi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Inflammation is part of the physiological response of the organism to infectious diseases caused by organisms such as bacteria, viruses, fungi, or parasites. Innate immunity, mediated by mononuclear phagocytes, including monocytes and macrophages, is a first line of defense against infectious diseases and plays a key role triggering the delayed adaptive response that ensures an efficient defense against pathogens. Monocytes and macrophages stimulation by pathogen antigens results in activation of different signaling pathways leading to the release of proinflammatory cytokines. However, inflammation can also participate in the pathogenesis of several diseases, the autoimmune diseases that represent a relevant burden for human health. Dendrimers are branched, multivalent nanoparticles with a well-defined structure that have a high potential for biomedical applications. To explore new approaches to fight against the negative aspects of inflammation, we have used neutral high-generation phosphorus dendrimers bearing 48 (G3) or 96 (G4) bisphosphonate groups on their surface. These dendrimers show no toxicity and have good solubility and chemical stability in aqueous solutions. Here, we present data indicating that neutral phosphorus dendrimers show impressive antiinflammatory activities both in vitro and in vivo. In vitro, these dendrimers reduced the secretion of proinflammatory cytokines from mice and human monocytederived macrophages. In addition, these molecules present efficient antiinflammatory activity in vivo in a mouse model of subchronic inflammation. Taken together, these data suggest that neutral G3-G4 phosphorus dendrimers have strong potential applications in the therapy of inflammation and, likely, of autoimmune diseases.dendrimers | inflammation | innate immunity | air pouch | macrophage

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“…For example, the anti-inflammatory manoalide and cacospongionolide B were isolated from the sponge Luffariella variabilis and Fasciospongia cavernosa, respectively [2,3]. A phospholipase A 2 -inhibitory compound, petrosaspongiolide M, was found from Petrosaspongia nigra [4].…”

Section: Introductionmentioning

confidence: 99%

Triple Inhibitory Activity of Cliona celata Against TNF-α-Induced Matrix Metalloproteinase-9 Production Via Downregulated NF-κB and AP-1, Enzyme Activity, and Migration Potential

et al. 2011

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Extracellular matrix-degrading protease, matrix metalloproteinase-9 (MMP-9), is known to be involved in vascular smooth muscle cell (SMC)'s aberrant proliferation and movement in atherosclerotic lesions. During screening of the MMP-9-inhibitory compounds from marine animal resources, we have found that the ethyl acetate extract from Cliona celata (ECC) effectively inhibits the SMC-derived MMP-9 enzyme activity and gene expression. In addition, the ECC effectively repressed the migration potential of the tumor necrosis factor-α (TNF-α)-stimulated human aortic smooth muscle cell (HASMC). As assessed by Western blot analysis, the produced MMP-9 protein levels in the TNF-α-induced HASMC were significantly decreased by the concomitant treatment of ECC at the 50- to 300-μg/mL concentration ranges. In addition, in the RT-PCR experiment, the expressed MMP-9 mRNA levels in the TNF-α-induced HASMC were seemingly decreased by ECC treatment at the same concentration ranges (50-300 μg/mL). For the action mechanism(s) of ECC to the phenotype changes in HASMC, we have further evaluated the ECC's pharmacological activities on the signal molecules which are importantly linked in the MMP-9 expression and cell migration potential of HASMC. We have found that extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation as a target point is suppressed by the ECC treatment in the TNF-α-treated HASMC. Using electrophoretic mobility shift assay, the nuclear extracts purified from ECC-treated HASMCs were shown to decrease the binding potentials on the labeled nuclear factor-kappaB (NF-κB) and activator protein 1 probes. NF-κB p65 and phosphorylated c-Jun contents were also decreased in the purified nuclear extracts from the ECC-treated HASMC, as confirmed by Western blot analysis. Finally, it was shown that the ECC-treated HASMCs were less migrated when compared to the TNF-α-treated cells, as confirmed by HASMC migration assays using the 8-μm pore transwell membranes. From these results, it was proposed that ECC has a potentially applicable anti-atherosclerotic activity.

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Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor‐α by inhibiting nuclear factor‐κB activation

Cited by 36 publications

References 35 publications

Glycerylprostaglandin Synthesis by Resident Peritoneal Macrophages in Response to a Zymosan Stimulus

Glycerylprostaglandin Synthesis by Resident Peritoneal Macrophages in Response to a Zymosan Stimulus

Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Triple Inhibitory Activity of Cliona celata Against TNF-α-Induced Matrix Metalloproteinase-9 Production Via Downregulated NF-κB and AP-1, Enzyme Activity, and Migration Potential

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