Clinical and Experimental Pharmacology and Physiology最新文献_第8页

Role of omega-6 and omega-3 fatty acids in fetal programming. -6和-3脂肪酸在胎儿编程中的作用。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-01-28 DOI: 10.1111/1440-1681.13244

Nirajan Shrestha, Simone L Sleep, James S M Cuffe, Olivia J Holland, Anthony V Perkins, Suk Yu Yau, Andrew J McAinch, Deanne H Hryciw

{"title":"Role of omega-6 and omega-3 fatty acids in fetal programming.","authors":"Nirajan Shrestha, Simone L Sleep, James S M Cuffe, Olivia J Holland, Anthony V Perkins, Suk Yu Yau, Andrew J McAinch, Deanne H Hryciw","doi":"10.1111/1440-1681.13244","DOIUrl":"https://doi.org/10.1111/1440-1681.13244","url":null,"abstract":"Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha-linolenic acid (ALA) are major omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n-6 PUFA has increased gradually worldwide, and elevated n-6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n-6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n-6 PUFA in fetal programming, the importance of a balance between n-6 and n-3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n-6 and n-3 PUFA contents in diets.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"907-915"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37496481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 41

Lithium attenuates d-amphetamine-induced hyperlocomotor activity in mice via inhibition of interaction between cyclooxygenase-2 and indoleamine-2,3-dioxygenase. 锂通过抑制环氧化酶-2和吲哚胺-2,3-双加氧酶之间的相互作用来减弱d-安非他明诱导的小鼠过度运动活性。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-01-24 DOI: 10.1111/1440-1681.13243

Dieu-Hien Phan, Eun-Joo Shin, Ji Hoon Jeong, Hai-Quyen Tran, Naveen Sharma, Bao Trong Nguyen, Tae Woo Jung, Seung-Yeol Nah, Kuniaki Saito, Toshitaka Nabeshima, Hyoung-Chun Kim

{"title":"Lithium attenuates d-amphetamine-induced hyperlocomotor activity in mice via inhibition of interaction between cyclooxygenase-2 and indoleamine-2,3-dioxygenase.","authors":"Dieu-Hien Phan, Eun-Joo Shin, Ji Hoon Jeong, Hai-Quyen Tran, Naveen Sharma, Bao Trong Nguyen, Tae Woo Jung, Seung-Yeol Nah, Kuniaki Saito, Toshitaka Nabeshima, Hyoung-Chun Kim","doi":"10.1111/1440-1681.13243","DOIUrl":"https://doi.org/10.1111/1440-1681.13243","url":null,"abstract":"In the present study, we investigated whether mood stabilizer lithium (Li) protects against d-amphetamine (AMP)-induced mania-like behaviours via modulating the novel proinflammatory potential. Repeated treatment with AMP resulted in significant increases in proinflammatory cyclooxygenase-2 (COX-2) and indolemaine-2,3-dioxygenase-1 (IDO)-1 expression in the prefrontal cortex (PFC) of mice. However, AMP treatment did not significantly change IDO-2 and 5-lipoxygenase (5-LOX) expression, suggesting that proinflammatory parameters such as COX-2 and IDO-1 are specific for AMP-induced behaviours. AMP-induced initial expression of COX-2 (15 minutes post-AMP) was earlier than that of IDO-1 (1 hour post-AMP). Mood stabilizer Li and COX-2 inhibitor meloxicam significantly attenuated COX-2 expression 15 minutes post-AMP, whereas IDO-1 inhibitor 1-methyl-DL-tryptophan (1-MT) did not affect COX-2 expression. However, AMP-induced IDO-1 expression was significantly attenuated by Li, meloxicam or 1-MT, suggesting that COX-2 is an upstream molecule for the induction of IDO-1 caused by AMP. Consistently, co-immunoprecipitation between COX-2 and IDO-1 was observed at 30 minutes, 1, 3, and 6 hours after the final AMP treatment. This interaction was also significantly inhibited by Li, meloxicam or 1-MT. Furthermore, AMP-induced hyperlocomotion was significantly attenuated by Li, meloxicam or 1-MT. We report, for the first time, that mood stabilizer Li attenuates AMP-induced mania-like behaviour via attenuation of interaction between COX-2 and IDO-1, and that the interaction of COX-2 and IDO-1 may be critical for the therapeutic intervention mediated by mood stabilizer.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"790-797"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37496501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Glaucocalyxin A inhibits hydrogen peroxide-induced oxidative stress and inflammatory response in coronary artery smooth muscle cells. 青花素A抑制过氧化氢诱导的冠状动脉平滑肌细胞氧化应激和炎症反应。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-01-31 DOI: 10.1111/1440-1681.13253

Shunming Zhu, Junbo Zhang, Ying Lv

{"title":"Glaucocalyxin A inhibits hydrogen peroxide-induced oxidative stress and inflammatory response in coronary artery smooth muscle cells.","authors":"Shunming Zhu, Junbo Zhang, Ying Lv","doi":"10.1111/1440-1681.13253","DOIUrl":"https://doi.org/10.1111/1440-1681.13253","url":null,"abstract":"Atherosclerosis is a complex chronic inflammatory disease that remains one of the leading causes of death and disability worldwide. A previous study reported that glaucocalyxin A (GLA), a natural ent-Kaurane diterpenoid triptolide, exhibits anti-atherosclerotic activity. However, the underlying molecular mechanism has not yet been explored. In the present study, we evaluated the anti-atherosclerotic effect of GLA and the underlying mechanism in vitro. Human coronary artery smooth muscle cells (HCASMCs) were stimulated by hydrogen peroxide (H2 O2 ) to induce oxidative stress and inflammation. The results showed that GLA pretreatment improved the viability of H2 O2 -induced HCASMCs. The increased reactive oxygen species production and decreased superoxide dismutase and glutathione peroxidase activities in H2 O2 -induced HCASMCs were reversed by GLA pretreatment. In addition, GLA treatment suppressed the H2 O2 -induced expression of inducible nitric oxide synthase, NADPH oxidase (NOX) 2, and NOX4 in HCASMCs. Moreover, treatment with GLA reduced the production of several inflammatory cytokines, including tumour necrosis factor-alpha, interleukin (IL)-6, and IL-1β in H2 O2 -induced HCASMCs. Furthermore, GLA treatment suppressed the phosphorylation of p38, as well as inactivating the NF-κB signalling pathway. These findings suggested that GLA protected against H2 O2 -induced oxidative stress and inflammation via inhibition of p38 phosphorylation and NF-κB activation in HCASMCs.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"765-770"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37522525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

An integrated RNA-Seq and network study reveals the effect of nicotinamide on adrenal androgen synthesis. 一项综合RNA-Seq和网络研究揭示了烟酰胺对肾上腺雄激素合成的影响。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2020-05-01 Epub Date: 2020-02-09 DOI: 10.1111/1440-1681.13258

Xueying Gao, Zhiheng Yu, Jie Yang, Yutong Gao, Shumin Li, Wei Zhang

{"title":"An integrated RNA-Seq and network study reveals the effect of nicotinamide on adrenal androgen synthesis.","authors":"Xueying Gao, Zhiheng Yu, Jie Yang, Yutong Gao, Shumin Li, Wei Zhang","doi":"10.1111/1440-1681.13258","DOIUrl":"https://doi.org/10.1111/1440-1681.13258","url":null,"abstract":"Acne vulgaris is a chronic inflammatory disease of the skin resulting from androgen-induced increased sebum production and altered keratinization. Nicotinamide (NAM), an amide form of vitamin B3 with a well-established safety profile, has shown good therapeutic potential in treating acne and its complications. NAM has anti-inflammatory effects and reduces sebum but its function in androgen biosynthesis remains unknown. In this study, we used a widely used cell model, starved human adrenal NCI-H295R cells, to examine the effects of NAM in androgen production and its mediated network changes. By treating NCI-H295R cells with 1-25 mmol/L of NAM, we found that cell viability was only slightly inhibited at the highest dose (25 mmol/L). NAM reduced testosterone production in a dose-dependent manner. Transcriptomic analysis demonstrated that key enzymes of androgen biosynthesis were significantly decreased under NAM treatment. In addition, gene set enrichment analysis (GSEA) showed that gene sets of cell cycle, steroid biosynthesis, TGFβ signalling, and targets of IGF1 or IGF2 were enriched in NAM-treated cells. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) analysis of the differentially expressed genes also suggested that steroidogenesis and SMAD signalling were affected by NAM. Overall, these crucial genes and pathways might form a complex network in NAM-treated NCI-H295R cells and result in androgen reduction. These findings help explain the potential molecular actions of NAM in acne vulgaris, and position NAM as a candidate for the treatment of other hyperandrogenic disorders.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"821-830"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37557548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Acute electrophysiologic effects of the polyphenols resveratrol and piceatannol in rabbit atria. 白藜芦醇和皮杉醇对兔心房急性电生理的影响。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2019-01-01 DOI: 10.1111/1440-1681.13005

Gerrit Frommeyer, Julian Wolfes, Christian Ellermann, Simon Kochhäuser, Dirk G Dechering, Lars Eckardt

引用次数: 7

Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang ameliorate ulcerative colitis via regulating the MAPKs and NF-κB pathways in dendritic cells. 从毛竹中提取果胶多糖(Lour.)Baill。海南姜通过调节树突状细胞的MAPKs和NF-κB通路改善溃疡性结肠炎。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2019-01-01 Epub Date: 2018-10-01 DOI: 10.1111/1440-1681.13026

Xin-Pu Miao, Xiao-Ning Sun, Qiong-Si Li, Lu-Jia Cui, Xuan-Yu Wang, Gui-Feng Zhuang, Tao-Zhi Deng

{"title":"Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang ameliorate ulcerative colitis via regulating the MAPKs and NF-κB pathways in dendritic cells.","authors":"Xin-Pu Miao, Xiao-Ning Sun, Qiong-Si Li, Lu-Jia Cui, Xuan-Yu Wang, Gui-Feng Zhuang, Tao-Zhi Deng","doi":"10.1111/1440-1681.13026","DOIUrl":"https://doi.org/10.1111/1440-1681.13026","url":null,"abstract":"This study was to investigate the effects and mechanisms of pectic polysaccharides (PP) extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). Eighty female BALB/c mice were randomly divided into four groups: Control, DSS, DSS + salicylazosulfapyridine (SASP), and DSS+ PP. The disease activity index (DAI), overall physical activity, and blood stool were monitored daily to evaluate severity of UC. Histological scores of the colon were observed. The expression of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways in colon tissues and bone marrow-derived dendritic cells (DCs) was assessed by western blot, immunohistochemistry, electrophoretic mobility shift assay (EMSA) and real time polymerase chain reaction (RT-PCR). Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The overall physical activity, DAI and histological scores decreased in DSS+SASP and DSS+PP groups, compared with the DSS-alone group. Also, tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) reduced significantly while the expression of IκBα was up-regulated, extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 were activated, in DSS+SASP and DSS+PP groups. PP inhibited activation of MAPKs and NF-κB pathways in the bone-marrow-derived DCs. In conclusion, PP significantly ameliorated murine DSS-induced UC model, via regulation of MAPKs and NF-κB pathways in DCs.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"46 1","pages":"48-55"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36424854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

The roles of PD-1/PD-L1 and its signalling pathway in gastrointestinal tract cancers. PD-1/PD-L1及其信号通路在胃肠道肿瘤中的作用

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2019-01-01 Epub Date: 2018-10-08 DOI: 10.1111/1440-1681.13028

Chunguo Cui, Bo Yu, Qi Jiang, Xingfang Li, Kaiyao Shi, Zecheng Yang

{"title":"The roles of PD-1/PD-L1 and its signalling pathway in gastrointestinal tract cancers.","authors":"Chunguo Cui, Bo Yu, Qi Jiang, Xingfang Li, Kaiyao Shi, Zecheng Yang","doi":"10.1111/1440-1681.13028","DOIUrl":"https://doi.org/10.1111/1440-1681.13028","url":null,"abstract":"Cancer immunotherapy has been increasingly applied in the treatment of advanced malignancies. Consequently, immune checkpoints have become a major concern. As PD-1 is an important immunomodulatory protein, the blockade of PD-1 and its ligand PD-L1 is a promising tumour immunotherapy for human carcinoma. In this review, we first discuss the role of the PD-1/PD-L1 interaction in gastrointestinal tract cancers. Targeting PD-1 and PD-L1 in immune cells and tumour cells may show remarkable efficiency in gastrointestinal tract cancers. Second, the PD-1/PD-L1-associated signalling pathway involved in cancer immunotherapy in gastrointestinal tract cancers is discussed. Most importantly, this review summarizes the PD-1/PD-L1-targeted immunotherapy combinations with relevant signalling pathways, which may result in a breakthrough for the treatment of gastrointestinal tract cancers, such as gastric cancer, colorectal cancer and liver cancer. Meanwhile, the review provides a deeper insight into the mechanism of checkpoint blockade immunotherapies.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"46 1","pages":"3-10"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36446824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Peripheral apelin mediates stress-induced alterations in gastrointestinal motor functions depending on the nutritional status. 外周apelin根据营养状况介导应激诱导的胃肠运动功能改变。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2019-01-01 Epub Date: 2018-10-16 DOI: 10.1111/1440-1681.13032

Mehmet Bülbül, Osman Sinen, V Nimet İzgüt-Uysal, Gökhan Akkoyunlu, Saffet Öztürk, Fatma Uysal

{"title":"Peripheral apelin mediates stress-induced alterations in gastrointestinal motor functions depending on the nutritional status.","authors":"Mehmet Bülbül, Osman Sinen, V Nimet İzgüt-Uysal, Gökhan Akkoyunlu, Saffet Öztürk, Fatma Uysal","doi":"10.1111/1440-1681.13032","DOIUrl":"https://doi.org/10.1111/1440-1681.13032","url":null,"abstract":"Exposure to stress induces gastrointestinal (GI) dysmotility. In rodents, acute restraint stress (ARS) inhibits gastric emptying (GE) and intestinal transit (IT) via central and peripheral corticotropin-releasing factor (CRF)-mediated pathways. Peripherally administered apelin-13 was shown to inhibit GI motor functions; moreover, stress-induced upregulation of gastric apelin content was demonstrated in rats suggesting that peripheral apelin may mediate stress-induced alterations in GI motility. We investigated the role of endogenous peripheral apelin in stress-induced GI dysfunction. GE, IT and gastro-duodenal fasting motility were measured in non-stressed (NS), CRF-injected and ARS-loaded rats. CRF and apelin receptor antagonists astressin or F13A was administered before ARS or peripheral CRF injection. Apelin and APJ receptor expressions were determined using immunohistochemistry and quantified by qRT-PCR. Double immunofluorescence was performed for enteric neuronal apelin. GE and IT were delayed by CRF and ARS. ARS-induced changes were attenuated by F13A, whereas astressin was ineffective. CRF-induced alterations in GE and IT were restored completely by astressin, while they were diminished by F13A. Antral phase III-like contractions were disturbed following ARS which were preserved by preadministration of astressin, but not F13A. CRF impaired gastric and duodenal fasting contractions, while these changes were not altered by F13A. ARS increased apelin expression in stomach and duodenum. Apelin immunoreactivity was detected in mucosa, smooth muscles and myenteric plexi, whereas dense APJ receptor expression was observed within tunica muscularis. APJ receptor was downregulated in rats fasted overnight. These results suggest that enteric apelin acts as an inhibitor stress mediator in the postprandial state.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"46 1","pages":"29-39"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36498480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Key mechanisms underlying netrin-1 prevention of impaired spatial and object memory in Aβ_1-42 CA1-injected rats. 神经网络-1预防a - β1-42 ca1注射大鼠空间和物体记忆受损的关键机制。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2019-01-01 Epub Date: 2018-09-03 DOI: 10.1111/1440-1681.13020

Elham Zamani, Mohsen Parviz, Mehrdad Roghani, Parvaneh Mohseni-Moghaddam

{"title":"Key mechanisms underlying netrin-1 prevention of impaired spatial and object memory in Aβ1-42 CA1-injected rats.","authors":"Elham Zamani, Mohsen Parviz, Mehrdad Roghani, Parvaneh Mohseni-Moghaddam","doi":"10.1111/1440-1681.13020","DOIUrl":"https://doi.org/10.1111/1440-1681.13020","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studies, much is still to be clarified on precise mechanisms of pathobiology, prevention modalities, disease course and cure. Netrin-1, a laminin family protein, is said to have anti-inflammatory and anti-apoptotic effects and has a key role in neurogenesis and morphogenesis of neural structures. Accordingly, this study was designed to investigate protective effects of bilateral intrahippocampal fissure microinjections of netrin-1 on memory impairment in rat model of AD. Concomitant administration of netrin-1 with amyloid beta 1-42 (Aβ1-42 ) improved cognitive dysfunction in novel object recognition task (NOR), ameliorated impaired spatial memory in Morris water maze (MWM) setting, increased neuronal density and reduced amyloid aggregation in rat AD model. Netrin-1 was also seen to prevent Aβ1-42 -induced caspase-3, caspase-7 and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. Therefore, based on the data reported here, netrin-1 may be a promising biologic therapeutic that addresses the memory and neuronal loss associated with AD.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"46 1","pages":"86-93"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36361805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Inflammatory cytokines tumour necrosis factor-α and interleukin-8 enhance airway smooth muscle contraction by increasing L-type Ca²⁺ channel expression. 炎性细胞因子肿瘤坏死因子-α和白细胞介素-8通过增加l型Ca2+通道表达增强气道平滑肌收缩。

4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2019-01-01 Epub Date: 2018-10-15 DOI: 10.1111/1440-1681.13030

Shengang Ding, Jie Zhang, Sheng Yin, Jingsen Lu, Min Hu, Juan Du, Junhao Huang, Bing Shen

{"title":"Inflammatory cytokines tumour necrosis factor-α and interleukin-8 enhance airway smooth muscle contraction by increasing L-type Ca2+ channel expression.","authors":"Shengang Ding, Jie Zhang, Sheng Yin, Jingsen Lu, Min Hu, Juan Du, Junhao Huang, Bing Shen","doi":"10.1111/1440-1681.13030","DOIUrl":"https://doi.org/10.1111/1440-1681.13030","url":null,"abstract":"Inflammation elevates intracellular calcium concentrations ([Ca2+ ]i ) in airway smooth muscle (ASM). The L-type Ca2+ channel (L-VDCC) plays an important role in regulating Ca2+ influx in ASM. However, the role of L-VDCC in the inflammatory cytokine-induced pathology of ASM remains unclear. In the present study, we used calcium imaging and isometric tension measurements to assess the role of L-VDCC in agonist-induced [Ca2+ ]i rise and the associated contractions in mouse ASM, and we used immunoblotting to identify L-VDCC protein expression levels in mouse ASM after exposure to tumour necrosis factor alpha (TNF-α) or interleukin-8 (IL-8). Our results showed that high-K+ - or carbachol-induced contractions of mouse ASM were significantly greater after pretreatment with TNF-α or IL-8 for 24 hours. Both verapamil and nifedipine, L-VDCC inhibitors, abolished this increased contraction induced by TNF-α or IL-8 pretreatment. Moreover, TNF-α treatment enhanced carbachol-induced Ca2+ influx in ASM cells, and this effect was abrogated by verapamil. Additionally, immunoblotting results showed that preincubation of mouse ASM with TNF-α or IL-8 also enhanced L-VDCC protein expression. On the basis of these findings, we concluded that proinflammatory cytokines, such as TNF-α and IL-8, increase the expression level of L-VDCC, which in turn contributes to augmented agonist-induced ASM contractions. This effect of inflammation on L-VDCC expression in ASM may be associated with airway hyper-responsiveness and involved in the development of asthma.","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"46 1","pages":"56-64"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36481719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12