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Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice

Mantani, Polyxeni T. LU ; Dunér, Pontus LU ; Bengtsson, Eva LU ; Ljungcrantz, Irena LU ; Sundius, Lena LU ; To, Fong LU ; Nilsson, Jan LU ; Björkbacka, Harry LU and Fredrikson, Gunilla Nordin LU (2018) In Journal of Biological Chemistry 293(18). p.6791-6801
Abstract

Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an... (More)

Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon- (INF-). In support of this observation, a 4-week-long treatment of young Apoe/ mice (at 10 –14 weeks of age) with an IL-25– blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe/ mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans.

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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
293
issue
18
pages
11 pages
publisher
ASBMB
external identifiers
  • scopus:85046623740
ISSN
0021-9258
DOI
10.1074/jbc.RA117.000292
language
English
LU publication?
no
id
90e07bdf-1bdd-4650-977c-a11c9433a25d
date added to LUP
2018-05-25 12:57:55
date last changed
2018-08-19 04:43:05
@article{90e07bdf-1bdd-4650-977c-a11c9433a25d,
  abstract     = {<p>Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon- (INF-). In support of this observation, a 4-week-long treatment of young Apoe/ mice (at 10 –14 weeks of age) with an IL-25– blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe/ mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans.</p>},
  author       = {Mantani, Polyxeni T. and Dunér, Pontus and Bengtsson, Eva and Ljungcrantz, Irena and Sundius, Lena and To, Fong and Nilsson, Jan and Björkbacka, Harry and Fredrikson, Gunilla Nordin},
  issn         = {0021-9258},
  language     = {eng},
  month        = {01},
  number       = {18},
  pages        = {6791--6801},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice},
  url          = {http://dx.doi.org/10.1074/jbc.RA117.000292},
  volume       = {293},
  year         = {2018},
}