TY - JOUR
T1 - Interleukin-12 and -23 blockade mitigates elastase-induced abdominal aortic aneurysm
AU - Yan, Huimin
AU - Hu, Ying
AU - Akk, Antonina
AU - Ye, Karen
AU - Bacon, John
AU - Pham, Christine T.N.
N1 - Funding Information:
The authors would like to thank Dr. Robert Thompson (Washington University) for the de-identified human AAA specimens. This work was supported in part by the VA Merit Review Award 1I01 BX002714 and NIH grants AR067491 and P30 AR073752. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the National Institutes of Health.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Macrophages play an important role in the inflammatory process that contributes to the development of abdominal aortic aneurysm (AAA). Studies of human and mouse AAA tissue reveal expanded populations of macrophages producing an abundance of pro-inflammatory cytokines, including TNF-α, IL-12p40 and high level of metalloprotease 9 (MMP-9) at the late stages of disease. Herein, we show that blockade of IL-12p40 in the early phase of aneurysm development suppresses macrophage expansion, inflammatory cytokine and MMP-9 production and mitigates AAA development. Since IL-12 and IL-23 are related cytokines that share the common p40 subunit, we also evaluate the effect of direct IL-23 blockade on the development of AAA. Specific IL-23p19 blockade prevents AAA progression with the same efficiency as IL-12p40 antagonism, suggesting that the efficacy of anti-IL-12p40 treatment may reflect IL-23 blockade. IL-12p40 and IL-23p19 are also abundantly expressed in human AAA tissue. Our findings have potential translational value since IL-12p40 and IL-23p19 antagonists already exist as FDA-approved therapeutics for various chronic inflammatory conditions.
AB - Macrophages play an important role in the inflammatory process that contributes to the development of abdominal aortic aneurysm (AAA). Studies of human and mouse AAA tissue reveal expanded populations of macrophages producing an abundance of pro-inflammatory cytokines, including TNF-α, IL-12p40 and high level of metalloprotease 9 (MMP-9) at the late stages of disease. Herein, we show that blockade of IL-12p40 in the early phase of aneurysm development suppresses macrophage expansion, inflammatory cytokine and MMP-9 production and mitigates AAA development. Since IL-12 and IL-23 are related cytokines that share the common p40 subunit, we also evaluate the effect of direct IL-23 blockade on the development of AAA. Specific IL-23p19 blockade prevents AAA progression with the same efficiency as IL-12p40 antagonism, suggesting that the efficacy of anti-IL-12p40 treatment may reflect IL-23 blockade. IL-12p40 and IL-23p19 are also abundantly expressed in human AAA tissue. Our findings have potential translational value since IL-12p40 and IL-23p19 antagonists already exist as FDA-approved therapeutics for various chronic inflammatory conditions.
UR - http://www.scopus.com/inward/record.url?scp=85069467224&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-46909-y
DO - 10.1038/s41598-019-46909-y
M3 - Article
C2 - 31320700
AN - SCOPUS:85069467224
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 10447
ER -