Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice
(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
- 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
- organization
- publishing date
- 2018-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 293
- issue
- 18
- pages
- 11 pages
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:85046623740
- pmid:29572351
- ISSN
- 0021-9258
- DOI
- 10.1074/jbc.RA117.000292
- language
- English
- LU publication?
- yes
- id
- 90e07bdf-1bdd-4650-977c-a11c9433a25d
- date added to LUP
- 2018-05-25 12:57:55
- date last changed
- 2024-01-14 20:48:14
@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 = {{American Society for Biochemistry and Molecular Biology}}, 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}}, doi = {{10.1074/jbc.RA117.000292}}, volume = {{293}}, year = {{2018}}, }