• BMB Reports
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• v.40 no.4
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• pp.562-570
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• 2007

Soluble or cell-bound IL-1 receptor accessory protein (IL-1RAcP) does not bind IL-1 but rather forms a complex with IL-1 and IL-1 receptor type I (IL-1RI) resulting in signal transduction. Synthetic peptides to various regions in the Ig-like domains of IL-1RAcP were used to produce antibodies and these antibodies were affinity-purified using the respective antigens. An anti-peptide-4 antibody which targets domain III inhibited 70% of IL-$1\beta$-induced productions of IL-6 and PGE2 from 3T3-L1 cells. Anti-peptide-2 or 3 also inhibited IL-1-induced IL-6 production by 30%. However, antipeptide-1 which is directed against domain I had no effect. The antibody was more effective against IL-$1\beta$ compared to IL-$1\alpha$. IL-1-induced IL-6 production was augmented by coincubation with PGE2. The COX inhibitor ibuprofen blocked IL-1-induced IL-6 and PGE2 production. These results confirm that IL-1RAcP is essential for IL-1 signaling and that increased production of IL-6 by IL-1 needs the co-induction of PGE2. However, the effect of PGE2 is independent of expressions of IL-1RI and IL-1RAcP. Our data suggest that domain III of IL-1RAcP may be involved in the formation or stabilization of the IL-1RI/IL-1 complex by binding to epitopes on domain III of the IL-1RI created following IL-1 binding to the IL-1RI.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.183-189
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• 1991

The present study was performed to elucidate the factors which modulate uterine prostaglandin synthesis during the implantation period in rats, by employing delayed implantation model. Administration of estradiol sharply increased uterine cAMP concentration 4 hrs later during the delayed implantation process. Concentrations of uterine PGE and $PGF_2{\alpha}$ were increased at 12 hrs after the estradiol treatment although an increase in $PGF_2{\alpha}$ was not statistically significant. The concomitant treatment of indomethacin with estradiol significantly suppressed estradiol-induced PGE and $PGF_2{\alpha}$ at 12 hrs, while uterine cAMP concentration was not suppressed. The treatment of dbcAMP without estradiol gradually increased uterine PGE and $PGF_2{\alpha}$ showing the maximum 8 hrs later, suggesting that cAMP minics estradiol effect on uterine prostaglandin synthesis during the implantation process. Furthermore, the pretreatment of theophylline, phosphodiesterase inhibitor, induced significantly greater concentrations of uterine PGE and $PGF_2{\alpha}$, compared with estradiol-only treated group. These results suggest that estradiol stimulates uterine prostaglandin synthesis and this process may be mediated by an elevation of cAMP during the delayed implantation process in rats.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.167-172
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• 2000

The purpose of this study is to develop a transurethral liquid suppository containing prostaglandin $E_1\;(PGE_1)-loaded$ microemulsion, which undergoes a phase transition to gels at body temperature. The effects of oils, ethanol as solvent and HCl as pH-controlling agent on the physicochemical properties of liquid suppositories composed of poloxamer P 407, P 188 and carbopol was investigated. The stability of $PGE_1$ and release of $PGE_1$ from liquid suppository were evaluated. Oils such as Neobee and soybean oil significantly decreased the gelation temperature but increased the gel strength of liquid suppository due to their strongly binding with the components of liquid suppository base. However, ethanol slightly did the opposite. The pH of liquid suppositories hardly affected the gelation temperature and gel strength due to addition of very small HCl (0.005-0.01%). A liquid suppository [$PGE_1/P$ 407/P 188/carbopol/Neobee/ethanol/HCl (0.2/14/14/0.4/7/2/0.005%)], which had the gelation temperature $(34.2{\pm}0.6^{\circ}C)$ and gel strength $(31.35{\pm}4.37\;sec)$ suitable for liquid suppository system, was easily administered and not leak out from the body. About 60% of $PGE_1$ was released out within 2 h from this formulation. It was shown that the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppository by Fickian diffusion. It was stable at $4^{\circ}C$ for at least 2 months. The results suggest that transurethral liquid suppository containing prostaglandin $E_1-loaded$ microemulsion is thought to be a convenient, safe and effective dosage form for $PGE_1$. However, it should be further developed as a more convenient and stable dosage form for $PGE_1$.

• Korean Journal of Plant Resources
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• v.33 no.4
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• pp.287-292
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• 2020

Lathyrus palustris often used as a treatment for inflammation of the kidneys in Korean traditional medication. Generally, drugs for arthritis have anti-inflammatory and antinociceptive properties. However, the validity of the anti-inflammatory effect has not been scientifically investigated so far. Therefore, the purpose of the research was to investigate the latent anti-inflammatory ability of L. palustris using the ethanol extract. To evaluate the anti-inflammatory activities, we examined the inflammatory arbitrators such as a nitric oxide (NO) and prostaglandin E₂ (PGE₂) on RAW 264.7 cells. Our results indicated that ethanol extract significantly inhibited the lipopolysaccharide E (LPS) derived PGE₂ production in RAW 264.7 cell. The inhibitory activity of ethanol extract for PGE₂ tests with inhibition ratio showed in 40 ㎍/mL. Overall, PGE₂ tests had a higher inhibitory effect on inflammation than NO tests. This result anticipated that the ethanol extract from L. palustris is a good candidate for developing the origin of anti-inflammatory agents.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.1013-1021
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• 1996

There are many important factors in periodontal inflammation. $IL-1{\beta}$, $PGE_2$ and collagenase are predorminantly key factors. These inflammatory mediators induce gingival tissue and alveolar bone destruction. For the prevention and treatment of periodontal disease, it is necessary to inhibit $IL-1{\beta}$, $PGE_2$ production and collagenase activity. Ursodeoxycholic acid(UDCA) has immunomodulatory properties, and there is evidence that some natural extracts show antiinflammatory activity to some degree. The purpose of this study was to assess the inhibitory effect of UDCA and its mixture with natural extracts on $IL-1{\beta}$, $PGE_2$ production and collagenase activity. Accordingly we assessed the effect of UDCA and its mixture combined with some natural extracts on inhibition of $IL-1{\beta}$, $PGE_2$ production and collagenase activity. For the $IL-l{\beta}$ inhibition study, cultured cells were exposed to $25{\mu}g/ml$ LPS. $IL-1{\beta}$ activity was measured by $IL-1{\beta}$ enzyme immunoassay system. Human gingival fibroblasts were prepared and cells (l05/well) were seeded into culture plates. $rhIL-1{\beta}$ was added to induce $PGE_2$. The amount of $PGE_2$ in sample media was measured using enzyme immunoassay system. Crude collagenase was prepared from Porphyromonas gingivalis and collagenolytic activity was determined using a Collageno kit CLN-100. The test inhibitor was added to the assay mixture consisting of 0.1ml of 50mM Tris buffer(pH 7.5) and 0.2ml of substrate solution. UDCA and UDCA combined with natural extracts generally inhibited $IL-1{\beta}$ production. groups above 0.01% UDCA strongly inhibited $IL-l{\beta}$ synthesis. Both groups inhibited $IL-1{\beta}-induced$ synthesis of $PGE_2$. In low concentration, the degree of inhibition was as same as prednisolone. In high concentration, each group was superior to prednisolone. UDCA group and UDCA mixture group exerted a moderate inhibition of collagenolytic enzyme. The present study suggested that UDCA and its mixture with natural extracts could be further investigated as antiinflammatory drug for periodontal disease.

• The Korean Journal of Physiology
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• v.14 no.2
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• pp.17-20
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• 1980

This study was undertaken to investigate the effect of the acidosis on the gastric acid secretion in the isolated whole stomach of the rat and the effect of prostaglandin $E_1$ on the gastric acid secretion influenced by the acidosis. Twenty-two male albino rats(Sprague-Dawley strain) were used. The isolated whole stomach from each rat was introduced into the Kreb's solution which was continuously gassed with $95%O_2-5%CO_2$ for 1 hour, after irrigation of the lumen with cold physiological saline$(4^{\circ}C)$. Thereafter, each stomach was irrigated again with 5% dextrose solution (pH 7.4, $37^{\circ}C$), and filled with the dextrose solution. All the stomachs with the dextrose solution were divided into 4 groups according to the Kreb's solutions in which each stomach was incubated for 30 min: 1) control group, in the pH 7.4 solution, 2) $PGE_1$ group, in the pH 7.4 solution containing $5\;{\mu}g/ml$ of $PGE_1$, 3) acid group, in the pH 7.0 solution, and 4) $acid+PGE_1$ group, in the pH 7.0 solution containing $5\;{\mu}g/ml$ of $PGE_1$. After incubatory period, the contents of each stomach were collected and centrifuged(1,500 rpm, room temperature) for 15 min. The acid output in the supernatant was determined with 0.012 N NaOH by means of autotitrator(Dosimat, Metrohm Herisau Co.) at pH 7.4. Results obtained were as follows: 1) The acid output of the acid group increased significantly in comparison with the control value. 2) The acid output of the $acid+PGE_1$ group decreased significantly in comparison with the acid group. It is inferred from the above results that the acidosis facilitates the gastric acid secretion and $PGE_1$ inhibits the gastric acid secretion induced by the acidosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9967-9972
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• 2014

In order to prove whether downregulation of COX-2 (Cyclooxygenase-2) could modulate the epithelial-mesenchymal transition (EMT) of breast cancer, celecoxib and siRNA were respectively used to inhibit COX-2 function and expression in MDA-MB-231 cells. The EMT reversal effect in the RNAi treated group was better than that of the celecoxib group while there were no obvious differences in the medium $PGE_2$ levels between the two groups. The results show that COX-2 pathways may contribute considerably to EMT of breast cancer cells, partially dependent on the PGE2 cascade. Akt2, ZEB2 and Snail were measured to clarify the underlying mechanisms of COX-2 on EMT; COX-2 may modulate EMT of breast cancer by regulating these factors. This finding may be helpful to elucidate the mechanisms of selective COX-2 inhibitor action in EMT modulation in breast cancer.

• Fisheries and Aquatic Sciences
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• v.6 no.3
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• pp.130-134
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• 2003

Proinflammatory effects of bacterial lipopolysaccharide (LPS) have been assessed by analysing the induction of two inflammatory genes, $interleukin-1\beta$ $(IL-1\beta)$ and cyclooxygenase-2 (COX-2), in rainbow trout (Oncorhynchus mykiss) macrophage cells. Production of a metabolite of arachidonic acid by COX-2, prostaglandin $E_2\;(PGE_2)$, was also analysed in macrophage cells after LPS stimulation. Northern blot analysis revealed that LPS $(5{\mu}g/mL)$ significantly upregulated $IL-1\beta$ (54 times) and COX-2 (40.7 times) gene expression in macrophage cells after 4 h stimulation. According to RT-PCR (Reverse Transcription Polymerase Chain Reaction) analysis, $IL-1\beta$ gene induction in LPS stimulated macrophage cells was started within 1h and significantly increased thereafter until 4h. Meanwhile, COX-2 gene induction by LPS was delayed in comparison with $IL-1\beta$ gene induction as a faint band was observed after 4h stimulation in head kidney macrophage cells. LPS also significantly increased $PGE_2$ production in head kidney leucocytes, presumably via activating COX-2 expression that metabolites arachidonic acid to $PGE_2$. In conclusion, it was demonstrated that LPS could induce two main inflammatory and immune related genes, $IL-1\beta$ and COX-2, and increase $PGE_2$ production in trout head kidney macrophage cells, representing a strong inflammatory activity.

• Bulletin of the Korean Chemical Society
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• v.31 no.2
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• pp.384-388
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• 2010

Human microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of prostaglandin $H_2$ ($PGH_2$) into prostaglandin $E_2$ ($PGE_2$). To establish a stable and efficient method to assess the activity of mPGES-1, a coupled enzyme assay system using mPGES-1, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and phosphomolybdic acid (PMA) was developed. In this assay system, $PGH_2$ was converted to $PGE_2$ by mPGES-1, and then $PGE_2$ was further transformed to the 15-keto-$PGE_2$ by 15-PGDH accompanying the production of NADH, which was easily detected by fluorescence spectrometry in a multi-well plate format. During the reaction, spontaneous oxidation of $PGH_2$ was prevented by PMA. Using this novel assay, the $K_m$ value of mPGES-1 for $PGH_2$ and the $IC_{50}$ value of the previously characterized inhibitor, MK-886, were determined to be 0.150 mM and $2.8\;{\mu}M$, respectively, which were consistent with the previously reported values. In addition, low backgrounds were observed in the multi-wall plate screening of chemical compounds.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.288-297
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• 2009

Objective : Inflammatory cytokines have a close relationship to insulin dependent diabetes mellitus (IDDM). The inhibitory effect of Smilacis Glabrae Rhizoma (SGR) were examined on production of nitric oxide (NO), prostaglandin $E_2$ $(PGE_2)$, synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and NF-${\kappa}$B activation in Raw 264.7 cells. Methods: Raw 264.7 cells were pretreated with SGR(20, 50, 100 ${\mu}g$/ml), and then cultured with lipopolysaccharides (LPS). Cell viability was measured by MTT assay; inhibition of NO, $PGE_2$, and TNF-${\alpha}$ production were measured by Griess reagent and enzyme-linked immunosorbent assay(ELISA). Induction of COX-2 and iNOS were determined by western blotting analysis. Inhibition of NF-${\kappa}$B was measured by immunofluorescence assay (IFA). Results: SGR inactivated NF-${\kappa}$B, and inhibited the production of NO, iNOS, and $PGE_2$. Inhibition of COX-2 and TNF-${\alpha}$ could not be confirmed. Conclusions: From the above result. SGR was found to have an anti-inflammatory effect of inhibition of NO, iNOS, and $PGE_2$ production via inhibition of NF-${\kappa}$B.