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

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.