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Intravenous immunoglobulin-mediated expansion of regulatory T cells in autoimmune patients is associated with increased prostaglandin E2 levels in the circulation

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Cellular & Molecular Immunology 2015年第5期12卷 650-652页

作者： Mohan S Maddur Jamma Trinath Magalie Rabin Francis Bolgert Moneger Guy Jean-Michel Vallat Laurent Magy Kithiganahalli N Balaji Srini V Kaveri Jagadeesh Bayry Institut National de la Sante et de la Recherche Medicale Paris France Centre de Recherche des Cordeliers Equipe - Immunopathology and Therapeutic Immunointervention Paris France Sorbonne Universites - UPMC Univ Paris 6 Paris France Universite Paris Descartes Paris France Department of Microbiology and Cell Biology Indian Institute of Science Bangalore India Centre de Reference 'Neuropathies Peripheriques Rares' et Service de Neurologie Hopital Universitaire Limoges Limoges France Reanimation Neurologique Neurologie 1 Hopital de la Pitie-Salpetriere Paris France International Associated Laboratory IMPACT (Institut National de la Sante et de la Recherche Medicale France -Indian Council of Medical Research India) National Institute of Immunohaematology Mumbai India

CD4＋FoxP3＋ regulatory T cells （Tregs） are immunosuppressive cells that are critical for immune tolerance. Several studies have demonstrated that one of the anti-inflammatory mechanisms of action of intravenous immunoglobulin （Wig） involves the expansion of Tregs. Recently, we demonstrated that IVIgmediated Treg expansion involves the cyclooxygenase-2 （COX-2）-dependent induction of prostaglandin E2 （PGE2） in human dendritic cells （DCs）. However, the validity of these findings in autoimmune patients is lacking.

关键词： associated increased prostaglandin

Association between the levels of prostaglandin E2 in tears and severity of dry eye

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International Journal of Ophthalmology(English edition) 2019年第7期12卷 1127-1133页

作者： Kaevalin Lekhanont Kanchalika Sathianvichitr Punyanuch Pisitpayat Thunyarat Anothaisintawee Kitipong Soontrapa Umaporn Udomsubpayakul Department of Ophthalmology Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok 10400 Thailand Department of Family Medicine Ramathibodi Hospital Mahidol University Bangkok 10400 Thailand Department of Pharmacology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok 10400 Thailand Clinical Epidemiology and Biostatistics Unit Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok 10400 Thailand

AIM: To investigate the relationship between the levels of prostaglandin E2(PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs.METHODS: Tear samples were collected from 36 non-Sj?gren syndrome dry eye patients(10 males and 26 females, mean age 50.11±11.17 y). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time(TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay(ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction(MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores(R=0.608, P<0.001), however, they did not significantly associate with TBUT(R=0.153, P=0.373), Schirmer scores(R=-0.098, P=0.570), ocular surface staining scores(R=0.282, P=0.095), and stage of MGD(R=-0.107, P=0.535).Male sex was significantly negatively correlated with tear PGE2 levels.CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.

关键词： dry eye prostaglandin E2 severity tear dryeye tests

Inhibitory effects of prostaglandin E₁ on activation of hepatic stellate cells in rabbits with schistosomiasis

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Hepatobiliary & Pancreatic Diseases International 2007年第2期6卷 176-181页

作者： WeiLong Zou Zhen Yang YunJin Zang DongJian Li ZhiPeng Liang ZhongYang Shen Institute of Transplantation General Hospital of the Chinese People's Armed Police Forces Beijing China. wlzouah@***

BACKGROUND: Liver fibrosis is the result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. At the cellular and molecular levels, this progressive process is mainly characterized by activation of hepatic stellate cells (HSCs). Schistosoma japonica is one of the most prevalent causes of liver fibrosis in China. It is characterized by hepatocyte damage, inflammation, and chronic parasite egg-induced granuloma formation leading to fibrosis. This study aimed to investigate the inhibitory effects of prostaglandin E1 (PGE1) on activation of HSCs and the alteration of type Ⅰ and Ⅲ collagen in rabbits with schistosomiasis. The study may promote the clinical application of praziquantel and PGE1 as a combined therapy to reverse hepatic fibrosis caused by schistosomiasis. METHODS: Rabbits were percutaneously infected with cercaria of S. japonicum. Seven rabbits were subjected to intravenous injections of PGE1 (2.5 μg/kg daily) from days 60 to 120 after infection. The ultrastructural changes in activated HSCs were observed under transmission electron microscopy. The expression of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Fibril-forming collagens were detected by picrosirius staining. RESULTS: Activation of HSCs was a characteristic alteration in schistosome-induced hepatic fibrosis. The expression of contraction-related α-SMA and thecontent of collagens were increased. Exogenous PGE1 markedly inhibited the activation of HSCs and reduced the expression of α-SMA around the hepatic sinusoids (P<0.01). The contents of type Ⅰ and Ⅲ collagens were significantly attenuated. The ratio of staining area to the whole field (10×3.3) under a polarized light microscope in the untreated and treated groups was 37.25±9.71 vs. 13.38±4.24 (P<0.01) and 9.66±3.52 vs. 6.23±1.81 (P<0.05), respectively. CONCLUSIONS: Activation of HSCs may play a key role in the progress of schistosome-induced hepatic fibrosis. PGE1 effectively protects rabbit liver from fibrosis, at le

关键词： hepatic fibrosis schistosome hepatic stellate cells prostaglandin E1 fibril-forming collagen

Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations

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World Journal of Gastroenterology 2019年第14期25卷 1753-1763页

作者： Yuichi Matsuno Junji Umeno Motohiro Esaki Yoichiro Hirakawa Yuta Fuyuno Yasuharu Okamoto Atsushi Hirano Shigeyoshi Yasukawa Fumihito Hirai Toshiyuki Matsui Shuhei Hosomi Kenji Watanabe Naoki Hosoe Haruhiko Ogata Tadakazu Hisamatsu Shunichi Yanai Shuji Kochi Koichi Kurahara Tsuneyoshi Yao Takehiro Torisu Takanari Kitazono Takayuki Matsumoto Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Department of Endoscopic Diagnostics and Therapeutic Saga University Hospital Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Department of Gastroenterology Fukuoka University Chikushi Hospital Department of Gastroenterology Osaka City University Graduate School of Medicine Department of Intestinal Inflammation Research Hyogo College of Medicine Center for Diagnostic and Therapeutic Endoscopy School of Medicine Keio University the Third Department of Internal Medicine Kyorin University School of Medicine Division of Gastroenterology Department of Internal Medicine Iwate Medical University Division of Gastroenterology Matsuyama Red Cross Hospital Department of Gastroenterology Sada Hospital

BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS). Crohn's disease(CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM) can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1. We measured the concentration of PGEMUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC) curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9 μg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval(CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with 95.0% sensitivity and 79.6% specificity.CONCLUSION PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

关键词： Chronic enteropathy associated with SLCO2A1 gene prostaglandin E major urinary metabolites Chronic nonspecific multiple ulcers of the small intestine Crohn's disease Small intestine

Research on the Status of Patent Protection of prostaglandin Analogues for Glaucoma in China

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Asian Journal of Social Pharmacy 2022年第2期17卷 178-185页

作者： Zhou Sheng’an Dong Li School of Business Administration Shenyang Pharmaceutical UniversityShenyang 110016China

Objective To study and analyze the status of patent protection of prostaglandin analogues for glaucoma in China.Methods Patent literatures published up to April 7,2020 were retrieved by the keywords“PG”and“prostaglandin”on such patent information service platforms as SIPO,SooPat,and IncoPat.And then they were statistically analyzed by qualitative and quantitative means.Results and Conclusion A total of 300 patent literature related to prostaglandin analogues for glaucoma were obtained,and most of them were invention patents,including patents for composition and dosage form,indications and uses,related synthesis,the compound,and composition preparations.prostaglandin analogues play an important role in the treatment of glaucoma.At present,China has a large number of patents applications,and the patent protection covers a wide range of technical fields,but the number of patents with valid legal status is relatively small.Therefore,China’s pharmaceutical enterprises and R&D institutions have more options in topic selection and project approval and patent protection strategies.

关键词： glaucoma prostaglandin patent protection

Effects of prostaglandin E_2 and all-trans retinoic acid combination on induced differentiation of human acute promyelocytic leukemia NB_4 cells

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Chinese Medical Journal 1997年第10期 48-53页

作者：陈子兴

Objective A human promyelocytic leukemia (APL) cell line NB 4 was used to demonstrate the synergistic effects between all trans retinoic acid (ATRA) and prostaglandin E 2 (PGE 2) on growth inhibition and cytodifferentiation induction. Methods NB 4 cells were cultured in the presence of either ATRA or PGE 2 as a single agent or in combinations at various ratio. Cell growth was measured and myeloid differentiation was tested on consecutive days over the whole course of culture. Results PGE 2 and ATRA synergistically induced the myeloid differentiation of NB 4 cells. In comparison with ATRA alone, the combination of PGE 2 with ATRA caused an almost 20 fold decrease of effective concentration of ATRA. Conclusion The combination of ATRA and PGE 2 at an appropriate ratio may provide a convenient oral regimen of combined differentiation therapy for a better clinical outcome in APL patients.

关键词： prostaglandin all-trans E2 Effects

The roles of prostaglandin F_(2) in regulating the expression of matrix metalloproteinase-12 via an insulin growth factor-2-dependent mechanism in sheared chondrocytes

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Signal Transduction and Targeted Therapy 2018年第1期3卷 30-42页

作者： Pei-Pei Guan Wei-Yan Ding Pu Wang College of Life and Health Sciences Northeastern UniversityShenyang 110819P.R.China

Osteoarthritis(OA)was recently identified as being regulated by the induction of cyclooxygenase-2(COX-2)in response to high fluid shear stress.Although the metabolic products of COX-2,including prostaglandin(PG)E2,15-deoxy-Δ^(12,14)-PGJ2(15d-PGJ2),and PGF_(2α),have been reported to be effective in regulating the occurrence and development of OA by activating matrix metalloproteinases(MMPs),the roles of PGF_(2α)in OA are largely overlooked.Thus,we showed that high fluid shear stress induced the mRNA expression of MMP-12 via cyclic(c)AMP-and PGF_(2α)-dependent signaling pathways.Specifically,we found that high fluid shear stress(20 dyn/cm2)significantly increased the expression of MMP-12 at 6 h(>fivefold),which then slightly decreased until 48 h(>threefold).In addition,shear stress enhanced the rapid synthesis of PGE2 and PGF_(2α),which generated synergistic effects on the expression of MMP-12 via EP2/EP3-,PGF_(2α)receptor(FPR)-,cAMP-and insulin growth factor-2(IGF-2)-dependent phosphatidylinositide 3-kinase(PI3-K)/protein kinase B(AKT),c-Jun N-terminal kinase(JNK)/c-Jun,and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)-activating pathways.Prolonged shear stress induced the synthesis of 15d-PGJ2,which is responsible for suppressing the high levels of MMP-12 at 48 h.These in vitro observations were further validated by in vivo experiments to evaluate the mechanisms of MMP-12 upregulation during the onset of OA by high fluid shear stress.By delineating this signaling pathway,our data provide a targeted therapeutic basis for combating OA.

关键词： prostaglandin Osteoarthritis matrix

Synthesis of 9-Halo prostaglandin Derivatives and Their Effect on Uterus Contraction

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Journal of Reproduction and Contraception 1998年第1期9卷 41-47页

作者：陈建兴陈海林曹霖陈良康 ShanghaiInstituteofPlannedParenthoodResearch Shanghai200032China ShanghaiInstituteofMateriaChineseAcademyofSciences Shanghai200031China

Four 9-halo prostaglandin derivatives were designed and synthesized. Their structures were confirmed by IR,~1HNMR, MS, etc. The effect on uterus contraction of ratswas studied in vitro. It was found that compound g-Br seemed to be the most sensitive andγ-Cl somewhat less, while a-Cl and a-Br had almost no action as compared with oxytocin(1 IU/ml).

关键词： 9-Halo prostaglandin Effect on uterus contraction

Expression and localization of prostaglandin receptors and stromal factors in human cervix—Variations in pregnant and non-pregnant states

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Open Journal of Molecular and Integrative Physiology 2013年第4期3卷 147-157页

作者： Chellakkan S. Blesson Nathalie Roos Olof Stephansson Britt Masironi Susann Reinert Ylva Vladic Stjernholm Gunvor Ekman-Ordeberg Lena Sahlin Division for Reproductive Endocrinology and the Pediatric Endocrinology Unit Department of Women’s and Children’s Health Karolinska University Hospital-Solna Karolinska Institutet Stockholm Sweden Division for Reproductive Endocrinology and the Pediatric Endocrinology Unit Department of Women’s and Children’s Health Karolinska University Hospital-Solna Karolinska Institutet Stockholm Sweden Division of Obstetrics and Gynecology Department of Women’s and Children’s Health Karolinska University Hospital-Solna Karolinska Institutet Stockholm Sweden Division of Obstetrics and Gynecology Department of Women’s and Children’s Health Karolinska University Hospital-Solna Karolinska Institutet Stockholm Sweden Division of Obstetrics and Gynecology Department of Women’s and Children’s Health Karolinska University Hospital-Solna Karolinska Institutet Stockholm Sweden Clinical Epidemiology Unit Department of Medicine Karolinska Institutet Stockholm Sweden

prostaglandins (PGs) mediate cervical ripening leading to parturition. PGs are used successfully to induce cervical ripening. However, the cell type specific expression of PG receptor subtypes and various stromal factors important for cervical ripening in human cervix is not known. Our objective was to investigate the expression and localization of PG receptors EP1-4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin ?B, ALOX12 (arachidonate 12-lipooxy-genase) and ALOX15 in human cervical tissue from pregnant and non-pregnant women. Cervical biopsies were obtained from non-pregnant (NP), term pregnant (TP) and post-partum (PP) women. The mRNA expression was determined with real-time PCR, protein expression and localization with immunohistochemistry. Our results show that the EP2 mRNA level was higher in the PP group as compared to TP, whereas the EP4 mRNA level was lower in the TP group as compared to NP. Concomitantly stromal EP2 and epithelial EP3 immunoreactivity was higher in the TP as compared to the NP group, while the EP4 immunostaining in glands was lower in the TP as compared to the PP group. Immunostaining of endothelial CTGF, smooth muscle furin and ALOX12, were all lower in the TP group as compared to NP, for CTGF also the PP group was lower than NP. Endothelial calgranulin B immunoreactivity was higher in the PP group than the NP group. PG receptors and stromal factors exhibit differential expression in the cervix from women in non-pregnant and pregnant states, implying their involvement in the process of cervical ripening.

关键词： Cervical Ripening Pregnancy Extracellular Matrix prostaglandin Receptors