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学科主题: 临床医学
题名:
Noncanonical cAMP pathway and p38 MAPK mediate beta(2)-adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts
作者: Yin, F1; Wang, YY1; Du, JH1; Lu, ZZ1; Han, CD1; Zhang, YY1
关键词: cytokines ; receptors ; protein kinases ; signal transduction
刊名: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
发表日期: 2006-03-01
DOI: 10.1016/j.yjmcc.2005.12.005
卷: 40, 期:3, 页:384-393
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Cell Biology
研究领域[WOS]: Cardiovascular System & Cardiology ; Cell Biology
关键词[WOS]: PROTEIN-KINASE-A ; NF-KAPPA-B ; CYCLIC-AMP ; PROINFLAMMATORY CYTOKINES ; INTERLEUKIN-6 FAMILY ; MYOCYTE HYPERTROPHY ; SIGNALING PATHWAY ; GENE-EXPRESSION ; ANGIOTENSIN-II ; STIMULATION
英文摘要:

We previously reported that cardiac fibroblasts, but not cardiomyocytes, are served as the predoininant source of IL-6 after isoproterenol stimulation in mouse myocardium. The present study investigated the molecular mechanism of isoproterenol-mediated secretion of IL-6 in Mouse cardiac fibroblasts. Treatment of cells with isoproterenol-induced a time-dependent accumlation of IL-6, which was mediated by beta(2)-adrenergic receptor (AR), the preponderant beta-AR Subtype in cardiac fibroblasts. Isoproterenol-induced secretion of IL-6 was mainly mediated by Gs-AC-cAMP signaling cascade and could be negatively regulated by Gi and PI3K. Surprisingly, the effect of cAMP was independent of protein kinase A and the exchange protein directly activated by cAMP (Epac)-Rap1 pathway and suggests the existence of a novel cAMP-dependent mechanism. p38 MAPK inhibitor SB203580, but not extracellular regulated protein kinase inhibitor, abrogated isoproterenol-induced IL-6 release in cardiac fibroblasts and mouse myocardium. Interestingly, p38 MAPK Could also be positively regulated by Gs-AC-cAMP but negatively regulated by Gi-PI3K pathway. Finally, Multiple transcription factors (AP-1, C/EBP, NF-kappa B and CREB) regulating the IL-6 gene are activated in response to isoproterenol stimulation, which may provide essential linkage between upstream cAMP-p38 MAPK signaling cascade and downstream IL-6 gene transcription. The present results suggest that beta(2)-AR mediates IL-6 production through a noncanonical cAMP responsible pathway and p38 MAPK. (c) 2006 Elsevier Ltd. All rights reserved.

语种: 英语
WOS记录号: WOS:000236059300007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51478
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China
2.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100083, Peoples R China

Recommended Citation:
Yin, F,Wang, YY,Du, JH,et al. Noncanonical cAMP pathway and p38 MAPK mediate beta(2)-adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2006,40(3):384-393.
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