Intravenous anesthetic propofol suppresses leukotriene production in murine dendritic cells

Inada, Takefumi; Ueshima, Hironobu; Shingu, Koh

doi:10.3109/1547691x.2012.712066

Cited by 5 publications

(6 citation statements)

References 45 publications

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“…We demonstrated that lesser amounts of LTB 4 , 5-HETE, 5-HpETE, 5S,6S-DiHETE, 5S,6R-DiHETE, and all-trans-LTB 4 were produced in the presence of propofol. The effect of propofol on LTB 4 was reported by Inada et al (36)(37)(38), and our result is compatible with theirs. 5S,6S-DiHETE, 5S,6R-DiHETE, and all-trans-LTB 4 are products of LTA 4 , which is produced via 5-LOX.…”

Section: Discussionsupporting

confidence: 94%

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B₄production

et al. 2017

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Propofol is an intravenous anesthetic that produces its anesthetic effect, largely the GABA receptor in the CNS, and also reduces the -formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B, we examined the effect of propofol on LTB production and Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid. Also, in the experiments on fMLP-stimulated neutrophils and 5-LOX-transfected human embryonic kidney cells, propofol attenuated the production of 5-LOX-related AA derivatives. Based on these results, we hypothesized that propofol would directly affect 5-LOX function. Using-azi-propofol (Azi), we photolabeled stable 5-LOX protein, which had been used to solve the X-ray crystallographic structure of 5-LOX, and examined the binding site(s) of propofol on 5-LOX. Two propofol binding pockets were identified near the active site of 5-LOX. Alanine scanning mutagenesis was performed for the residues of 5-LOX in the vicinity of propofol, and we evaluated the functional role of these pockets in LTB production. We demonstrated that these pockets were functionally important for 5-LOX activity. These two pockets can be used to explore a novel 5-LOX inhibitor in the future.-Okuno, T., Koutsogiannaki, S., Ohba, M., Chamberlain, M., Bu, W., Lin, F.-Y., Eckenhoff, R. G., Yokomizo T., Yuki, K. Intravenous anesthetic propofol binds to 5-lipoxygenase and attenuates leukotriene B production.

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Section: Discussionsupporting

confidence: 94%

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B₄production

et al. 2017

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“…Propofol itself does not change the availability of AA (the substrate of COX/5-LOX enzymes) or the expression levels of the enzymes; rather, it appears that propofol directly suppresses the activity of the COX/5-LOX. Suppression in a cell-free system with COX/5-LOX recombinant enzymes provided the evidence that propofol impacts directly on COX/5-LOX activity (Inada et al, 2013;Kubo et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, this is the first report to show that propofol imparts COX/5-LOX inhibiting effects in vivo. In vitro studies had previously shown that propofol had COX/ 5-LOX-inhibiting effects in a variety of cells (Inada et al, 2010(Inada et al, , 2013Kambara et al, 2009;Kubo et al, 2011). Propofol itself does not change the availability of AA (the substrate of COX/5-LOX enzymes) or the expression levels of the enzymes; rather, it appears that propofol directly suppresses the activity of the COX/5-LOX.…”

Section: Discussionmentioning

confidence: 99%

“…Also, due to its phenol-based structure, propofol has long been thought to have an anti-inflammatory effect (Vasileiou et al, 2009). Indeed, in vitro studies have indicated that propofol suppressed prostaglandin (PG) E 2 and leukotriene (LT) production (Inada et al, , 2013; this could partially explain the observed anti-inflammatory effect. These anti-cyclooxygenase (COX) and anti-5-lipoxygenase (5-LOX) properties of propofol could have far-reaching implications in clinical settings because these enzymes are involved in a variety of inflammatory states, including neuroinflammation (Teismann & Ferger, 2001;Manev et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Intravenous anesthetic propofol suppresses prostaglandin E₂and cysteinyl leukotriene production and reduces edema formation in arachidonic acid-induced ear inflammation

Inada

Hirota

Shingu

2014

Journal of Immunotoxicology

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Propofol is an intravenous drug widely used for anesthesia and sedation. Previously, propofol was shown to inhibit cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activities. Because these enzyme-inhibiting effects have only been demonstrated in vitro, this study sought to ascertain whether similar effects might also be observed in vivo. In the current studies, effects of propofol were tested in a murine model of arachidonic acid-induced ear inflammation. Specifically, propofol -as a pre-treatment -was intraperitoneally and then topical application of arachidonic acid was performed. After 1 h, tissue biopsies were collected and tested for the presence of edema and for levels of inflammatory mediators. The results indicated that the administration of propofol significantly suppressed ear edema formation, tissue myeloperoxidase activity, and tissue production of both prostaglandin E 2 and cysteinyl leukotrienes. From the data, it can be concluded that propofol could exert anti-COX and anti-5-LOX activities in an in vivo model and that these activities in turn could have, at least in part, suppressed arachidonic acid-induced edema formation in the ear.

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“…Beyond that, DCs can produce cytokines, leukotrienes, and prostanoids to regulate immune response as well. Research has reported that propofol suppresses prostaglandin E2 production from DCs by inhibiting the activity of COX enzyme (Inada et al, 2011), but the impact is limited to DCs, with no influence on IL-12/IL-10 production and T-cell proliferation. Leukotrienes can include cysteinyl leukotrienes (CysLTs) and leukotriene B4 (LTB4 ).…”

Section: Dendritic Cellsmentioning

confidence: 99%

The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes

Pan²,

Wang³

et al. 2022

Front. Pharmacol.

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Anesthetics are essential for cancer surgery, but accumulated research have proven that some anesthetics promote the occurrence of certain cancers, leading to adverse effects in the lives of patients. Although anesthetic technology is mature, there is no golden drug selection standard for surgical cancer treatment. To afford the responsibility of human health, a more specific regimen for cancer resection is indeed necessary. Immunosuppression in oncologic surgery has an adverse influence on the outcomes of patients. The choice of anesthetic strategies influences perioperative immunity. Among anesthetics, propofol has shown positive effects on immunity. Apart from that, propofol’s anticancer effect has been generally reported, which makes it more significant in oncologic surgery. However, the immunoregulative function of propofol is not reorganized well. Herein, we have summarized the impact of propofol on different immunocytes, proposed its potential mechanism for the positive effect on cancer immunity, and offered a conceivable hypothesis on its regulation to postoperative inflammation. We conclude that the priority of propofol is high in oncologic surgery and propofol may be a promising immunomodulatory drug for tumor therapy.

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Intravenous anesthetic propofol suppresses leukotriene production in murine dendritic cells

Cited by 5 publications

References 45 publications

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B₄production

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B₄production

Intravenous anesthetic propofol suppresses prostaglandin E₂and cysteinyl leukotriene production and reduces edema formation in arachidonic acid-induced ear inflammation

The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes

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Intravenous anesthetic propofol suppresses leukotriene production in murine dendritic cells

Cited by 5 publications

References 45 publications

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B4production

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B4production

Intravenous anesthetic propofol suppresses prostaglandin E2and cysteinyl leukotriene production and reduces edema formation in arachidonic acid-induced ear inflammation

The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes

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Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B₄production

Intravenous anesthetic propofol binds to 5‐lipoxygenase and attenuates leukotriene B₄production

Intravenous anesthetic propofol suppresses prostaglandin E₂and cysteinyl leukotriene production and reduces edema formation in arachidonic acid-induced ear inflammation