유도 분만에서 ProstaglandinE2의 경관내 삽입 및 질좌제의 임상적 효과 비교

상미란(Mi Lan Sang),권용일(Yong Il Kwon),박태철(Tae Chul Park),권동진(Dong Jin Kwon),이용석(Yong Suk Lee),배태욱(Tae Wook Bae),이진우(Jin Woo Lee),김수평(Su Pyung Kim) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.10

목적: 임신말기 유도 분만에 있어 Parity 및 Bishop-score에 따라 endocervical PGE2 및 vaginal PGE2의 임상적 효과를 비교하여 endocervical PGE2가 경관 숙화 및 분만유도에 더 효과적이라고 판단되어 본 연구를 시행하였다. 방법: 1998년 3월부터 9월까지 가톨릭 대학교 부속 의정부 성모병원 산부인과에 입원한 65명 산모를 대상으로 무작위로 추출하여 Parity 및 Bishop-score에 따라 3mg Dinoprostone을 경관내 및 질 후원개부위에 8시간 간격으로 최고 3개까지 삽입하여 규칙적인 진통이 유발될때까지 시행하였다. 결과: endocervical PGE2가 경관숙화 및 분만유도에 있어 더 확연한 효과를 보였다. 나이, 임신주수, 분만력, 초기 경관숙화정도는 두 군에 차이가 없었고 제왕절개율, 태아가사, 자궁과수축, 부작용도 차이가 없었다. 진통시작까지 걸린 시간에서 경산부에서 endocervical PGE2를 삽입한 경우가 다른 군보다 유의하게(p=0.0195) 짧았고 active labor까지 가는데 걸리는 시간은 초산부에서 endocervical PGE2를 삽입한 경우가 다른군보다 유의하게(p=0.0245) 짧았다. 또한 경산부에서 진통 시작까지 걸린 시간과 active labor까지 가는데 걸리는 시간, B-score 8점까지 되는데 걸린시간이 통계적으로 유의하게 짧았다. 요소간 분석을 보면 분만력, oxytocin등이 영향을 미칠 수 있고 그 중 투여방법이 가장 중요한 요인으로 추정되었다. 결론: 본 실험에서 경관 숙화가 안된 경우에 유도분만에 있어서 PGE2의 경관내 주입이 질정보다 효과가 좋으며 태아곤란증이나 제왕 절개분만, 신생아에 대한 영향에 차이가 없는 것으로 종합하여 보면 PGE2의 경관내 투여는 권장할 만한 가치가 있으며, 효과적인 유도분만에 유용하리라 사료된다. Objectives: The trial was performed to obtain an unbiased comparison of the relative merits of endocervical and vaginal prostaglandin E2(PGE2) in the case of parous and nulliparous woman with favorable and unfavorable cervical features. This study was performed to determine the clinical usefullness of endocervical PGE2 comparing with the vaginal PGE2 in cervical ripening and induction of labor. Method: The randomized trial with 65 Participants was performed with sealed envelopes for parity and Bishop score (from March to september, 1998). PGE2 tablet(3mg Dinoprostone) was administrated intravaginally to the 32 pregnant women and endocervically to the 33 pregnant women every eight hours with maximum three times until the regular labor develped. Result: Outcomes of labor and delivery were clearly related to cervical score at trial entry. endocerval PGE2 had a more marked effect on cervical ripeness than did vaginal PGE2. There were no significant differences on age distribution, gestatioanal period, primiparity, cervical status, initial B-score in each group. There were no significant differences in cesarian section rate, fetal distress, uterine hyperstimulation, side effect and poor infant outcome between the groups The mean induction time was statistically shorter in cervical group with multiparous women than other group(p=0.0195). In the induction-active labor time, cervical with primi group was statistically shorter than other group(p=0.0245). Statistically significant differences were noted between the nulliparous woman and multiparous women in mean induction time, induction-active labor time, time to B-score 8. In the factor that effects induction-active labor, route was significantly better than other factor.(p=0.0001) Conclusion: edocervical PGE2 is more effctive than vaginal PGE2 in cervical ripening and induction of active labor. the endocervical PGE2 resulted in a significantly shorter induction to active labor time compared with vaginal PGE2 and has almost no side effect. Because differences in effectiveness between endocervical and vaginal PGE2 are marginal, preference of woman and clinicians can the choice between them.

Thymoquinone (TQ) regulates cyclooxygenase-2 expression and prostaglandin E2 production through PI3kinase (PI3K)/p38 kinase pathway in human breast cancer cell line, MDA-MB-231

Yu, Seon-Mi,Kim, Song-Ja The Korean Society for Integrative Biology 2012 Animal cells and systems Vol.16 No.4

Thymoquinone (TQ), a drug extracted from the black seeds of Nigella sativa, has been shown to exhibit anti-inflammatory, anti-oxidant, and anti-neoplastic effects in numerous cancer cells. The effects of TQ on cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production in MDA-MB-231, however, remain poorly understood. Western blot analysis and immunofluorescence staining were performed to study the expression levels of inflammation regulatory proteins in MDA-MB-231. $PGE_2$ assay was conducted to explore the TQ-induced production of $PGE_2$. In this study, we investigated the effects of TQ on COX-2 expression and $PGE_2$ production in MDA-MB-231. TQ significantly induced COX-2 expression and increased $PGE_2$ production in a dose-dependent manner, as determined by a Western blot analysis and $PGE_2$ assay. Furthermore, the activation of Akt and p38 kinase, respectively, was up-regulated in TQ treated cells. Inhibition of p38 kinase with SB203580 and PI3kinase (PI3K) with LY294002 abolished TQ-caused COX-2 expression and decreased $PGE_2$ production. These results collectively demonstrate that TQ effectively modulates COX-2 expression and $PGE_2$ production via PI3K and p38 kinase pathways in the human breast cancer cell line MDA-MB-231.

사람 정상 코점막 상피세포에서 겔 형성 점소(Gel-Forming Mucin)분비에 대한 Prostaglandin E₂의 효과

김진국,김창훈,김규보,장현종,김현직,윤주헌 대한이비인후과학회 2006 대한이비인후과학회지 두경부외과학 Vol.49 No.3

Background and Objectives:Recently, Prostaglandin E2 (PGE2) was found to induce MUC5AC production via an agonist of E-prostanoid (EP2/EP4), but not EP1/EP3, in normal human airway epithelium. However, the receptor that mediates MUC5AC has not been determined. This study was aimed to investigate the MUC5AC mucin gene and mucin secretion by PGE2 and its receptors in cultured normal human nasal epithelial cells. Materials and Method:After treatment with PGE2 and/or PGE2 antagonist, gel-forming mucin mRNA expression was determined by reverse transcription-polymerase chain reaction. Total mucin and MUC5AC mucin levels were measured using an immuno-dot blotting assay. Results:PGE2 increased the MUC5AC gene expressions and MUC5AC mucin, but not the expressions of other gel-forming mucin genes. An EP2 receptor antagonist (AH6809) did not suppress the PGE2-induced MUC5AC gene expression or MUC5AC mucin. However, an EP4 receptor antagonist (AH23848) significantly suppressed the level of PGE2-induced MUC5AC gene expression and MUC5AC mucin. Conclusion:These findings indicate that PGE2 induces MUC5AC gene expression and mucin secretion via EP4 receptor in cultured normal human nasal epithelialcells. (Korean J Otolaryngol 2006;49:307-12)

Thymoquinone (TQ) regulates cyclooxygenase-2 expression and prostaglandin E2 production through PI3kinase (PI3K)/p38 kinase pathway in human breast cancer cell line, MDA-MB-231

유선미,김송자 한국통합생물학회 2012 Animal cells and systems Vol.16 No.4

Thymoquinone (TQ), a drug extracted from the black seeds of Nigella sativa, has been shown to exhibit antiinflammatory,anti-oxidant, and anti-neoplastic effects in numerous cancer cells. The effects of TQ on cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production in MDA-MB-231, however, remain poorly understood. Western blot analysis and immunofluorescence staining were performed to study the expression levels of inflammation regulatory proteins in MDA-MB-231. PGE2 assay was conducted to explore the TQ-induced production of PGE2. In this study, we investigated the effects of TQ on COX-2 expression and PGE2 production in MDA-MB-231. TQ significantly induced COX-2 expression and increased PGE2 production in a dose-dependent manner, as determined by a Western blot analysis and PGE2 assay. Furthermore, the activation of Akt and p38kinase, respectively, was up-regulated in TQ treated cells. Inhibition of p38 kinase with SB203580 and PI3kinase (PI3K) with LY294002 abolished TQ-caused COX-2 expression and decreased PGE2 production. These results collectively demonstrate that TQ effectively modulates COX-2 expression and PGE2 production via PI3K and p38kinase pathways in the human breast cancer cell line MDA-MB-231.

PMA에 의한 cyclooxygenase-2 발현 및 prostaglandin E₂의 생성 증가에 미치는 톳 추출물의 영향

박철(Cheol Park),최영현(Yung Hyun Choi) 한국생명과학회 2009 생명과학회지 Vol.19 No.10

본 연구에서는 갈조류의 일종인 톳(H. fusiforme)의 항염증 효과에 관한 생화학적 기전 해석을 위하여 U937 단핵구 세포를 이용하였으며, PMA에 의하여 인위적으로 유발된 COX-2의 발현 및 PGE₂의 생성 증가에 미치는 몇 가지 톳 추출물의 영향을 조사하였다. PMA는 U937 세포에서 처리 농도 의존적으로 COX-2의 전사 및 번역수준의 발현을 증가시켰으나, COX-1의 발현에는 큰 변화가 없었다. PAM에 의한 COX-2의 발현 증가는 PGE₂ 생성 증가와 연관성이 있었고, 톳의 열수 추출물에 비하여 에탄올 및 메탄올 추출물은 COX-2의 발현 증가는 PGE₂ 생성 증가를 매우 억제시켰으나, COX-1의 발현에는 영향을 주지 않았다. 아울러 PMA에 의한 NF-κB의 핵내 이동 및 IκB의 분해를 톳의 에탄올 및 메탄올 추출물이 완벽하게 차단시켰다. 본 연구의 결과는 톳의 에탄올 및 메탄올 추출물이 NF-κB의 활성을 차단함으로서 COX-2의 발현 및 PGE₂ 생성을 저해하였음을 의미하며, 이는 톳이 강력한 항염증 효능을 가지고 있음을 뒷받침하여 주는 것이다. Hizikia fusiforme is a kind of edible brown seaweed that grows mainly in the northwest Pacific including Korea, Japan and China, and has been widely used as food in Korea. Induction of cyclooxygenase-2 (COX-2) expression and prostaglandin E₂ (PGE₂) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In this study, we investigated the effects of extracts of H. fusiforme on the expression of COX-2 and production of PGE₂ in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate 13-acetate (PMA) to mimic inflammation, methanol extract of H. fusiforme (MEHF) and ethanol extract of H. fusiforme (EEHF), but not water extract of H. fusiforme (WEHF), inhibited PMA-induced expression of both COX-2 protein and mRNA, which was associated with inhibition of PGE₂ production. To investigate the mechanism by which MEHF and EEHF inhibit COX-2 gene expression and PGE₂ production, we examined the activation of nuclear factor-kappaB (NF-κB) in U937 cells. Pre-treatment with MEHF and EEHF significantly attenuated the PMA-induced IkappaB degradation and prevented nuclear translocation of NF-κB. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of H. fusiforme.

RAW264.7 대식세포에서 풀솜대 추출물의 nitric oxide 및 prostaglandin E₂생성 저해효과

남정환,서종택,김율호,김기덕,유동림,이종남,홍수영,김수정,손황배,김현삼,김보성,이경태,박희준,Nam, Jung-Hwan,Seo, Jong-Taek,Kim, Yul-Ho,Kim, Ki-Deog,Yoo, Dong-Lim,Lee, Jong-Nam,Hong, Su-Young,Kim, Su-Jeong,Sohn, Hwang-Bae,Kim, Hyun-Sam,Kim, B 한국식물생명공학회 2014 식물생명공학회지 Vol.41 No.4

본 연구에서는 풀솜대(Smilacina japonica)의 전초를 이용하여 세포독성 및 항염증 활성 효과를 평가하였다. 대식세포인 RAW264.7 cell에서 염증 매개 물질인 lipopo-lysacchride (LPS)로 염증을 유발시켜 nitric oxide (NO)와 prostaglandin $E_2$ ($PGE_2$) 같은 염증 유발인자들의 억제효과를 확인하였다. 풀솜대 chloroform 분획물의 염증 유발인자 억제 시 $IC_{80}$ value를 측정하였을 때 nitric oxide 및 prostaglandin $E_2$ 생성을 농도의존적으로 현저하게 저해하는 농도는 각각 53.3과 $32.5{\mu}g/ml$이었다. 따라서 본 연구 결과는 풀솜대의 chloroform과 같은 비극성용매 분획물들이 유의성 있는 항염증 효과를 나타내었으며, 이러한 효능은 예방의학적 가능성을 충분히 가지고 있기에 염증성질환의 예방을 위한 건강 기능성식품의 개발 가능성을 제시할 수 있을 것으로 기대된다. 또한 염증과 관련된 사이토카인 및 단백질 발현 메커니즘에 대한 추가적인 연구가 필요할 것으로 판단된다. Smilacina japonica is a localized common rhizomatous flowering plant, This plant is often used in Korean traditional systems of medicine as a remedy for migrain, diplegia, physical impurity, blood circulation, abscess and contusion. Generally drugs that are used for arthritis have antinociceptive and anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of S. japonica using the ethanolic extract and its subfractions. To evaluate the anti-inflammatory effects, we examined the inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) on RAW 264.7 macrophages. Our results indicated that hexane fraction significantly inhibited the LPS induced NO and $PGE_2$ production in the cells. The hexane fractions inhibitory activity for NO tests with $IC_{50}$ values showed in $53.3{\mu}g/ml$ and $PGE_2$ tests with $IC_{50}$ values showed at $32.5{\mu}g/ml$. Theseis result suggest a potential role of hexane fraction from S. japonica as source of anti-inflammatory agent.

Identification of a Novel PGE₂ Regulated Gene in SNU1 Gastric Cancer Cell

Park, Min-Seon,Kim, Hong-Tae,Min, Byung-Re,Kimm, Ku-Chan,Nam, Myeong-Jin 생화학분자생물학회 2000 Journal of biochemistry and molecular biology Vol.33 No.2

Prostaglandin $E_2$ ($PGE_2$) plays an important role in the regulation of various gastric functions, and the growth-inhibitory activities on tumor cells are studied in vitro and in vivo. Although the mechanisms have attracted many researchers in the past decade, the molecular mechanisms of cell cycle arrest, or induction of apoptosis by $PGE_2$, is unclear. We investigated the effects of $PGE_2$ on the growth of the human gastric carcinoma cell line SNU1 and genes that are regulated by $PGE_2$ and isolated them using differential display RT-PCR (DD RT-PCR). FACS analysis suggested that SNU1 cells were arrested at the G1 phase by $PGE_2$ treatment. This growth inhibitory effect was in a time- and dose-dependent manner. Treatment of SNU1 cells with $10\;{\mu}g/ml$ $PGE_2$, followed by DD RT-PCR analysis, revealed differently expressed bands patterns from the control. Among the differently expressed clones, we found an unidentified cDNA clone (HGP-27) overexpressed in $PGE_2$-treated cells. The full-length cDNA of HGP-27 was isolated using RACE, which consisted of a 30-nt 5'-noncoding region, a 891-nt ORF encoding the 296 amino acid protein, and a 738-nt 3'-noncoding region including a poly(a) signal. This gene was localized on the short arm of chromosome number 11. Using the Motif Finder program, a myb-DNA binding repeat signature was detected on the ORF region. The COOH-terminal half was shown to have similarity with the $NH_3$-terminal domain of thioredoxin (Trx). This relation between HGP-27 and Trx implied a potential role for HGP-27 in modulating the DNA binding function of a transcription factor, myb.

보중익기탕(補中益氣湯)이 접촉성 과민반응에 미치는 영향(影響)

박양구,정명,복영옥,이진호,강석훈,임규상,윤용갑,Park, Yang-Gu,Jung, Myung,Bok, Young-Ok,Lee, Jin-Ho,Kang, Suk-Hoon,Lim, Kyu-Sang,Yun, Young-Gab 대한한방안이비인후피부과학회 2016 한방안이비인후피부과학회지 Vol.29 No.1

Objective : The water extract of Bojungikgi-tang (BTE) composed with Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Atractylodes Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Cimicifuga Rhizoma, and Bupleuri Radix and it has been traditionally used for chronic diseases or weakness after illness in oriental countries. However, little is known about the effects of aqueous extract of BTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS). Therefore, the aim of this study was to investigate the effects of BTE on TMA-induced CHS in BALB/c mice.Methods : In this study, the extract of BTE was prepared by extracting with distilled water at 100℃ for 2.5 h. The extract was freeze-dried following filtration through 0.45 μm filter. Mice were orally administrated with or without BTE extract of different doses (25-200 ㎎/㎏/day) for 28 days. During the challenge period, mice were externally applied with different doses of BTE extract one time per day 30 min before TMA treatment. I examined the effects of BTE on the serum levels of IgE, IgG1, IgG2a, and IgG2b, nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in isolated peritoneal macrophages, Th2 cytokine production in isolated spleen cells, ear swelling responses, and the leukocyte infiltration induced by TMA.Results : The orally and externally administration of BTE dose-dependently reduced the serum levels of hapten-specific immunoglobulin E (IgE), IgG1 titer, and PGE₂ production as well as ear swelling responses and leukocyte infiltration in TMA-induced BALB/c mice. The levels of NO and PGE₂ production from peritoneal macrophages stimulated with TMA-BSA were markedly suppressed by pretreatment with BTE in a concentration dependent manner. Furthermore, the levels of Th2 cytokines (IL-4, IL-5, IL-13) production from spleen cells stimulated with ConA were markedly suppressed by BTE treatment in a concentration dependent manner.Conclusions : These results suggest that BTE treatment suppresses chronic contact hypersensitivity, and it can be assumed that the suppression of ear swelling, serum IgE, NO and PGE₂ levels, leukocyte infiltration, and Th2 cytokines in an animal model. Therefore, these properties may contribute to the strong anti-CHS response effect of BTE.

RAW264.7 대식세포에서 장대나물 추출물의 Nitric oxide 및 Prostaglandin E2생성 저해효과

남정환,서종택,김율호,김기덕,유동림,이종남,홍수영,김수정,손황배,김현삼,김보성,신지선,이경태,박희준 한국자원식물학회 2015 한국자원식물학회지 Vol.28 No.5

본 연구에서는 장대나물(Arabis glabra)의 전초를 이용하여세포독성 및 항염증 활성 효과를 평가하였다. 대식세포인 RAW264.7 cell에서 염증 매개 물질인 lipopo-lysacchride (LPS)로 염증을유발시켜 nitric oxide (NO)와 prostaglandi nE2 (PGE2) 같은 염증 유발인자들의 억제효과를 확인하였다. 장대나물의 hexane 과 chloroform 분획물의 염증 유발인자 억제 시 IC50 value를 측정하였을 때 nitric oxide 및 prostaglandin E2 생성을 농도의존적으로 현저하게 저해하는 농도는 각각 21.0과 18.0 ㎍/㎖였다. 따라서 본 연구 결과는 장대나물의 hexane, chloroform과 같은비극성용매 분획물들이 유의성 있는 항염증 효과를 나타내었으며, 이러한 효능은 예방의학적 가능성을 충분히 가지고 있기에염증성질환의 예방을 위한 건강 기능성식품의 개발 가능성을제시할 수 있을 것으로 기대된다. 또한 염증과 관련된 사이토카인 및 단백질 발현 메커니즘에 대한 추가적인 연구가 필요할 것으로 판단된다. Arabis glabra is a localized common rhizomatous flowering plant, This plant is often used in Korean traditional systems of medicine as a remedy for blood cleaning, detoxification, abscess, gastrospasm, arthritis, contraction and diarrhea. Generally drugs that are used for arthritis have antinociceptive and anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of A. glabra using the ethanolic extract and its sub-fractions. To evaluate the anti-inflammatory effects, we examined the inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) on RAW 264.7macrophages. Our results indicated that hexane and chloroform fraction significantly inhibited the LPSinduced NO and PGE2 production in the cells. The hexane fraction inhibitory activity for NO tests with IC50 values showed in 21.0 ㎍/㎖. The chloroform fraction inhibitory activity for PGE2 tests with IC50 values showed in 18.0 ㎍/㎖. These efficacy are expected to be able to present the potential for the development of health functional food for the prevention inflammatory diseases because it has sufficient preventive medical possibilities. Further, it is determined that it is necessary to further study the mechanism of cytokine and protein expression associated with inflammation.

Clostridium difficile Toxin A Upregulates Bak Expression through PGE2 Pathway in Human Colonocytes

( Young Ha Kim ),( Ho Kim ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.10

Clostridium difficile toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 (PGE₂) produced in response to toxin A stimulation. However, the molecular mechanism by which PGE₂ mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, PGE₂-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on PGE₂ production, and further showed that this effect was recapitulated by an Prostaglandin E2(PGE2) receptor-1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves PGE₂-upregulation of Bak through the EP1 receptor.