The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy
Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of...
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The Company of Biologists
2018-03-01
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doaj-f642af46e27748c4a22c1ef40abf39dc2020-11-24T21:11:17ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112018-03-0111310.1242/dmm.031708031708The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsyTao-Ran Li0Yan-Jie Jia1Chao Ma2Wen-Ying Qiu3Qun Wang4Xiao-Qiu Shao5Rui-Juan Lv6 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing, 100050, China Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing, 100050, China Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College,1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College,1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing, 100050, China Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing, 100050, China Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing, 100050, China Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of inflammatory signaling occurring in TLE. To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells. We found that enhancive miR-146a could upregulate the expression of IL-1β and downregulate the expression of CFH, whereas reductive miR-146a could downregulate the expression of IL-1β and upregulate the expression of CFH, in hippocampi of chronic TLE rat models. Meanwhile, enhancive miR-146a could increase the abnormal wave forms in the chronic TLE rat models. Additionally, enhancive IL-1β could feedback downregulate the expression of CFH, upregulate the expression of miR-146a and increase the abnormal wave forms in chronic TLE rat models. After CFH gene knockdown in U251 cells, enhancive miR-146a did not upregulate the expression of IL-1β. In summary, this study shows that enhancive miR-146a can upregulate the inflammatory factor IL-1β in chronic TLE by downregulating CFH, and that upregulation of IL-1β plays an important feedback-regulating role in the expression of miR-146a and CFH, forming a miR-146a–CFH–IL-1β loop circuit that initiates a cascade of inflammation and then leads to the perpetuate inflammation in TLE. Therefore, modulation of the miR-146a–CFH–IL-1β loop circuit could be a novel therapeutic target for TLE.http://dmm.biologists.org/content/11/3/dmm031708Temporal lobe epilepsyInflammationInterleukin-1βComplement factor HMicroRNA-146a |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tao-Ran Li Yan-Jie Jia Chao Ma Wen-Ying Qiu Qun Wang Xiao-Qiu Shao Rui-Juan Lv |
spellingShingle |
Tao-Ran Li Yan-Jie Jia Chao Ma Wen-Ying Qiu Qun Wang Xiao-Qiu Shao Rui-Juan Lv The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy Disease Models & Mechanisms Temporal lobe epilepsy Inflammation Interleukin-1β Complement factor H MicroRNA-146a |
author_facet |
Tao-Ran Li Yan-Jie Jia Chao Ma Wen-Ying Qiu Qun Wang Xiao-Qiu Shao Rui-Juan Lv |
author_sort |
Tao-Ran Li |
title |
The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy |
title_short |
The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy |
title_full |
The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy |
title_fullStr |
The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy |
title_full_unstemmed |
The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy |
title_sort |
role of the microrna-146a/complement factor h/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8403 1754-8411 |
publishDate |
2018-03-01 |
description |
Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of inflammatory signaling occurring in TLE. To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells. We found that enhancive miR-146a could upregulate the expression of IL-1β and downregulate the expression of CFH, whereas reductive miR-146a could downregulate the expression of IL-1β and upregulate the expression of CFH, in hippocampi of chronic TLE rat models. Meanwhile, enhancive miR-146a could increase the abnormal wave forms in the chronic TLE rat models. Additionally, enhancive IL-1β could feedback downregulate the expression of CFH, upregulate the expression of miR-146a and increase the abnormal wave forms in chronic TLE rat models. After CFH gene knockdown in U251 cells, enhancive miR-146a did not upregulate the expression of IL-1β. In summary, this study shows that enhancive miR-146a can upregulate the inflammatory factor IL-1β in chronic TLE by downregulating CFH, and that upregulation of IL-1β plays an important feedback-regulating role in the expression of miR-146a and CFH, forming a miR-146a–CFH–IL-1β loop circuit that initiates a cascade of inflammation and then leads to the perpetuate inflammation in TLE. Therefore, modulation of the miR-146a–CFH–IL-1β loop circuit could be a novel therapeutic target for TLE. |
topic |
Temporal lobe epilepsy Inflammation Interleukin-1β Complement factor H MicroRNA-146a |
url |
http://dmm.biologists.org/content/11/3/dmm031708 |
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