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Interleukin‐6 enhances matrix metalloproteinase‐14 expression via the RAF–mitogen‐activated protein kinase kinase–extracellular signal‐regulated kinase 1/2–activator protein‐1 pathway
Author(s) -
Feng Min,
Cai XiaoJun,
Zhang Wei,
Liu XiaoLing,
Chen Liang,
Zhang Yun,
Zhang MingXiang,
Zhang Mei
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05246.x
Subject(s) - kinase , microbiology and biotechnology , protein kinase a , matrix metalloproteinase , signal transduction , activator (genetics) , extracellular matrix , mapk/erk pathway , small interfering rna , apolipoprotein e , mitogen activated protein kinase kinase , biology , chemistry , cancer research , medicine , biochemistry , receptor , rna , disease , gene
Summary 1. Interleukin (IL)‐6 is a pivotal cytokine that regulates extracellular matrix (ECM) metabolism by increasing collagen degradation via activation of matrix metalloproteinases (MMPs), such as MMP‐14. In the present study, we investigated the role of IL‐6 in atherosclerotic plaque and signalling pathways in apolipoprotein E‐deficient (ApoE −/− ) mice. 2. Twenty‐five male ApoE −/− mice were fed a high‐fat diet and atherosclerotic lesions in the right common carotid artery were induced by perivascular placement of a constrictive collar. Immunohistochemical analysis detected expression of IL‐6 and MMP‐14 in atherosclerotic lesions of the right common carotid artery. 3. On silencing activator protein (AP)‐1 expression with a specific small interfering RNA, 75% of the IL‐6‐induced increase in MMP‐14 expression was abolished through the RAF–mitogen‐activated protein kinase kinase–extracellular signal‐regulated kinase 1/2–AP‐1 pathway. 4. These findings suggest a novel molecular pathway for inflammation‐associated ECM dysregulation, which may account for atherosclerotic plaque rupture.