The role of IL-6 in pathogenesis of abdominal aortic aneurysm in mice

• DOI: 10.1371/journal.pone.0185923
• Publication Date: 2017-10-05T17:48:41Z
• Authors: Michihide Nishihara; Hiroki Aoki; Satoko Ohno; Aya Furusho; Saki Hirakata; Norifumi Nishida; Sohei Ito; Makiko Hayashi; Tsutomu Imaizumi; Yoshihiro Fukumoto
• Keywords: 0301 basic medicine; Interleukin-6; Science; Q; R; Antibodies, Neutralizing; Receptors, Interleukin-6; Disease Models, Animal; Mice; 03 medical and health sciences; Medicine; Animals; Transcriptome; Research Article; Aortic Aneurysm, Abdominal; Signal Transduction

Although the pathogenesis of abdominal aortic aneurysm (AAA) remains unclear, evidence is accumulating to support a central role for inflammation. Inflammatory responses are coordinated by various soluble cytokines of which IL-6 is one of the major proinflammatory cytokines. In this study we examined the role of IL-6 in the pathogenesis of experimental AAA induced by a periaortic exposure to CaCl2 in mice. We now report that the administration of MR16-1, a neutralizing monoclonal antibody specific for the mouse IL-6 receptor, mildly suppressed the development of AAA. The inhibition of IL-6 signaling provoked by MR16-1 also resulted in a suppression of Stat3 activity. Conversely, no significant changes in either NFκB activity, Jnk activity or the expression of matrix metalloproteinases (Mmp) -2 and -9 were identified. Transcriptome analyses revealed that MR16-1-sensitive genes encode chemokines and their receptors, as well as factors that regulate vascular permeability and cell migration. Imaging cytometric analyses then consistently demonstrated reduced cellular infiltration for MR16-1-treated AAA. These results suggest that IL-6 plays an important but limited role in AAA pathogenesis, and primarily regulates cell migration and infiltration. These data would also suggest that IL-6 activity may play an important role in scenarios of continuous cellular infiltration, possibly including human AAA.