Macrophage differentiation in abdominal aortic aneurysm via IL-6 signals

• Project/Area Number: 22791264
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Kurume University
• Principal Investigator: OHNO Satoko 久留米大学, 医学部, 助教 (80569418)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 血管外科学 / 大動脈瘤 / サイトカイン / 大動脈解離 / 血管 / 分子生物学

Research Abstract

In this project, we investigated the hypothesis that IL-6/JAK/STAT pathway is activated and involved in the pathogenesis of abdominal aortic aneurysm(AAA), using human AAA tissue culture and mouse model of AAA. We found that human AAA tissue secrets large amount of IL-6 in culture media, and JAK/STAT pathway is involved in the secretion of a subset of inflammatory cytokines. We also found that JAK/STAT pathway is activated in mouse model of AAA during the rapid expansion of the diameter. However, macrophage-specific deletion of SOCS3 gene(mSOCS3-KO), which should enhance the IL-6 signal, did not affect the formation of AAA in mice. Unexpectedly, mSOCS3-KO showed greater susceptibility to acute aortic dissection(AAD) upon the angiotensin II infusion compared to wild type mice. Thus, macrophage IL-6 signal appears to be dispensable for AAA development, but essential to AAD development in mouse models.

Research Products

• [Journal Article] Hepatocyte growth factor promotes ananti-inflammatory cytokine profile in humanabdominal aortic aneurysm tissue (2011)
  • Author(s): Shintani, Y., Nishihara, M., OhnoS., Furusho, A., Aoki, H., Hiromatsu, S-i., Akashi, H., Imaizumi, T., Aoyagi, S.
  • Journal Title: Atherosclerosis Volume: Vol.216 Pages: 307-12
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor promotes an anti-inflammatory cytokine profile in human abdominal aortic aneurysm tissue (2011)
  • Author(s): Shintani, Y., Nishihara, M., Ohno, S., Furusho, A., Aoki, H., Hiromatsu, S.-i., Akashi, H., Imaizumi, T., Aoyagi, S.
  • Journal Title: Atherosclerosis Volume: 216 Pages: 307-12
  • Peer Reviewed
• [Presentation] Macrophage IL-6 signaling is criticallyinvolved in the pathogenesis of acute aorticdissection (2012)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, SakiHirakata, Norifumi Nishida, Hideo Yasukawa, and Tsutomu Imaizumi
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-18
• [Presentation] Macrophage IL-6 signaling is critically involved in the pathogenesis of acute aortic dissection (2012)
  • Author(s): 大野聡子
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: マリンメッセ福岡(福岡県)
  • Year and Date: 2012-03-18
• [Presentation] JAK/STAT pathway is highly active andregulates a subset of cytokines in abdominalaortic aneurysm (2011)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Tsutomu Imaizumi
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-03
• [Presentation] JAK/STAT系による大動脈瘤のサイトカインネットワーク制御 (2010)
  • Author(s): 大野聡子、青木浩樹、西原通秀、今泉勉
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] JAK/STAT系による大動脈瘤のサイトカインネットワーク制御 (2010)
  • Author(s): 大野聡子
  • Organizer: 第33回日本高血圧学会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] ヒト大動脈瘤組織におけるマトリクス・メタロプロテアーゼ系の発現パターン解析 (2010)
  • Author(s): 西原通秀、青木浩樹、大野聡子、今泉勉
  • Organizer: 第33回日本高血圧学会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15