IL-6 knockout mice are protected from cocaine-induced kindling behaviors; possible involvement of JAK2/STAT3 and PACAP signalings
DC Field | Value | Language |
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dc.contributor.author | Huynh Nhu Mai | - |
dc.contributor.author | Chung, Yoon Hee | - |
dc.contributor.author | Shin, Eun-Joo | - |
dc.contributor.author | Sharma, Naveen | - |
dc.contributor.author | Jeong, Ji Hoon | - |
dc.contributor.author | Jang, Choon-Gon | - |
dc.contributor.author | Saito, Kuniaki | - |
dc.contributor.author | Nabeshima, Toshitaka | - |
dc.contributor.author | Reglodi, Dora | - |
dc.contributor.author | Kim, Hyoung-Chun | - |
dc.date.available | 2019-03-07T04:40:11Z | - |
dc.date.issued | 2018-06 | - |
dc.identifier.issn | 0278-6915 | - |
dc.identifier.issn | 1873-6351 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/2117 | - |
dc.description.abstract | IL-6 has been recognized as an anticonvulsant against certain neuroexcitotoxicities. We aimed to investigate on the interactive role between IL-6 and PACAP in cocaine-induced kindling behaviors. Although we found that cocaine (45 mg/kg, i.p./day x 5) significantly increased IL-6 and TNF-alpha expression, it resulted in a decrease in IFN-gamma expression. We observed that the cocaine-induced increase in IL-6 expression was more pronounced than that in TNF-alpha expression. Genetic depletion of IL-6 significantly activated cocaine kindling behaviors. This phenomenon was also consistently observed in WT mice that received a neutralizing IL-6 receptor antibody. Cocaine-treated IL-6 knockout mice exhibited significantly decreased PACAP and PACAP receptor (PAC1R) mRNA levels and significantly increased TNF-alpha gene expression. TNF-alpha knockout mice were protected from cocaine kindling via an up-regulation of IL-6, phospho-JAK2/STAT3, PACAP, and PAC1R levels, which produced anti-apoptotic effects. Recombinant IL-6 protein (rIL-6, 2 mu g, i.v./mouse/day x 5) also up-regulated phospho-JAK2/STAT3, PACAP, and PAC1R mRNA levels, leading to anti-apoptotic effects in IL-6 knockout mice. Consistently, AG490, a JAK2/STAT3 inhibitor, and PACAP 6-38, a PAC1 receptor antagonist, counteracted rIL-6-mediated protection. Combined, our results suggest that IL-6 gene requires up-regulation of phospho-JAK2/STAT3, PACAP, and PAC1R and down-regulation of the TNF-alpha gene to modulate its anticonvulsive/neuroprotective potential. | - |
dc.format.extent | 15 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.title | IL-6 knockout mice are protected from cocaine-induced kindling behaviors; possible involvement of JAK2/STAT3 and PACAP signalings | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.fct.2018.04.031 | - |
dc.identifier.bibliographicCitation | FOOD AND CHEMICAL TOXICOLOGY, v.116, pp 249 - 263 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000433656100028 | - |
dc.identifier.scopusid | 2-s2.0-85046159604 | - |
dc.citation.endPage | 263 | - |
dc.citation.startPage | 249 | - |
dc.citation.title | FOOD AND CHEMICAL TOXICOLOGY | - |
dc.citation.volume | 116 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | Cocaine-induced kindling (convulsive) behaviors | - |
dc.subject.keywordAuthor | Interleukin-6 knockout mice | - |
dc.subject.keywordAuthor | Pituitary adenylate cyclase-activating polypeptide | - |
dc.subject.keywordAuthor | JAK2/STAT3 | - |
dc.subject.keywordAuthor | Tumor necrosis factor-alpha knockout mice | - |
dc.subject.keywordAuthor | Hippocampus | - |
dc.subject.keywordPlus | CYCLASE-ACTIVATING POLYPEPTIDE | - |
dc.subject.keywordPlus | TRIMETHYLTIN-INDUCED NEUROTOXICITY | - |
dc.subject.keywordPlus | INTERLEUKIN-1 RECEPTOR ANTAGONIST | - |
dc.subject.keywordPlus | SYMPATHETIC-NERVE ACTIVITY | - |
dc.subject.keywordPlus | INCREASED PLASMA-LEVELS | - |
dc.subject.keywordPlus | ACID-INDUCED SEIZURES | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | KAINIC-ACID | - |
dc.subject.keywordPlus | HIPPOCAMPAL-NEURONS | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.relation.journalResearchArea | Food Science & Technology | - |
dc.relation.journalResearchArea | Toxicology | - |
dc.relation.journalWebOfScienceCategory | Food Science & Technology | - |
dc.relation.journalWebOfScienceCategory | Toxicology | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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