Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways
Apolipoprotein CIII (apo CIII), a small glycoprotein that binds to the surfaces of certain lipoproteins, is associated with inflammatory and atherogenic responses in vascular cells. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory biomarker and potential therape...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2015-07-01
|
| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/4/5/661 |
| _version_ | 1819101840016408576 |
|---|---|
| author | Xiaolei Han Tiedong Wang Jifeng Zhang Xingxing Liu Zhuang Li Gangqi Wang Qi Song Daxin Pang Hongsheng Ouyang Xiaochun Tang |
| author_facet | Xiaolei Han Tiedong Wang Jifeng Zhang Xingxing Liu Zhuang Li Gangqi Wang Qi Song Daxin Pang Hongsheng Ouyang Xiaochun Tang |
| author_sort | Xiaolei Han |
| collection | DOAJ |
| description | Apolipoprotein CIII (apo CIII), a small glycoprotein that binds to the surfaces of certain lipoproteins, is associated with inflammatory and atherogenic responses in vascular cells. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory biomarker and potential therapeutic target for cardiovascular disease (CVD). Here, we report that apo CIII increases Lp-PLA2 mRNA and protein levels in dose- and time- dependent manner in human monocytic THP-1 cells, and the increase can be abolished by MAPK and NFκB pathway inhibitors. Lp-PLA2 inhibitor, 1-linoleoyl glycerol attenuates the inflammation induced by apo CIII. In turn, exogenous Lp-PLA2 expression upregulates apo CIII and the upregulation can be inhibited by 1-linoleoyl glycerol in HepG2 cells. Moreover, plasma Lp-PLA2 level is correlated with apo CIII expression in pig liver. In vivo, Lp-PLA2 expression in monocytes and its activity in serum were significantly increased in human apo CIII transgenic porcine models compared with wild-type pigs. Our results suggest that Lp-PLA2 and apo CIII expression level is correlated with each other in vitro and in vivo. |
| first_indexed | 2024-12-22T01:25:03Z |
| format | Article |
| id | doaj.art-c9be875d71734e1faf5915fc289a5be2 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-22T01:25:03Z |
| publishDate | 2015-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-c9be875d71734e1faf5915fc289a5be22022-12-21T18:43:38ZengThe Company of BiologistsBiology Open2046-63902015-07-014566166510.1242/bio.201410900201410900Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathwaysXiaolei Han0Tiedong Wang1Jifeng Zhang2Xingxing Liu3Zhuang Li4Gangqi Wang5Qi Song6Daxin Pang7Hongsheng Ouyang8Xiaochun Tang9 Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun 130062, China Apolipoprotein CIII (apo CIII), a small glycoprotein that binds to the surfaces of certain lipoproteins, is associated with inflammatory and atherogenic responses in vascular cells. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory biomarker and potential therapeutic target for cardiovascular disease (CVD). Here, we report that apo CIII increases Lp-PLA2 mRNA and protein levels in dose- and time- dependent manner in human monocytic THP-1 cells, and the increase can be abolished by MAPK and NFκB pathway inhibitors. Lp-PLA2 inhibitor, 1-linoleoyl glycerol attenuates the inflammation induced by apo CIII. In turn, exogenous Lp-PLA2 expression upregulates apo CIII and the upregulation can be inhibited by 1-linoleoyl glycerol in HepG2 cells. Moreover, plasma Lp-PLA2 level is correlated with apo CIII expression in pig liver. In vivo, Lp-PLA2 expression in monocytes and its activity in serum were significantly increased in human apo CIII transgenic porcine models compared with wild-type pigs. Our results suggest that Lp-PLA2 and apo CIII expression level is correlated with each other in vitro and in vivo.http://bio.biologists.org/content/4/5/661Apolipoprotein CIIILipoprotein-associated phospholipase A2MAPK pathwayNFκB pathwayInflammation |
| spellingShingle | Xiaolei Han Tiedong Wang Jifeng Zhang Xingxing Liu Zhuang Li Gangqi Wang Qi Song Daxin Pang Hongsheng Ouyang Xiaochun Tang Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways Biology Open Apolipoprotein CIII Lipoprotein-associated phospholipase A2 MAPK pathway NFκB pathway Inflammation |
| title | Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways |
| title_full | Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways |
| title_fullStr | Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways |
| title_full_unstemmed | Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways |
| title_short | Apolipoprotein CIII regulates lipoprotein-associated phospholipase A2 expression via the MAPK and NFκB pathways |
| title_sort | apolipoprotein ciii regulates lipoprotein associated phospholipase a2 expression via the mapk and nfκb pathways |
| topic | Apolipoprotein CIII Lipoprotein-associated phospholipase A2 MAPK pathway NFκB pathway Inflammation |
| url | http://bio.biologists.org/content/4/5/661 |
| work_keys_str_mv | AT xiaoleihan apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT tiedongwang apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT jifengzhang apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT xingxingliu apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT zhuangli apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT gangqiwang apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT qisong apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT daxinpang apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT hongshengouyang apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways AT xiaochuntang apolipoproteinciiiregulateslipoproteinassociatedphospholipasea2expressionviathemapkandnfkbpathways |