title: Atherosclerosis severity is not affected by a deficiency in IL-33/ST2 signaling.
abstract: Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work demonstrated that the systemic administration of recombinant IL-33 reduces the development of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice by inducing a Th1-to-Th2 shift. The objective of our study was to examine the role of endogenous IL-33 and ST2 in atherosclerosis. ApoE(-/-), IL-33(-/-)ApoE(-/-), and ST2(-/-)ApoE(-/-) mice were fed with a cholesterol-rich diet for 10 weeks. Additionally, a group of ApoE(-/-) mice was injected with a neutralizing anti-ST2 or an isotype control antibody during the period of the cholesterol-rich diet. Atherosclerotic lesion development was measured by Oil Red O staining in the thoracic-abdominal aorta and the aortic sinus. There were no significant differences in the lipid-staining area of IL-33(-/-)ApoE(-/-), ST2(-/-)ApoE(-/-), or anti-ST2 antibody-treated ApoE(-/-) mice, compared to ApoE(-/-) controls. The absence of IL-33 signaling had no major and consistent impact on the Th1/Th2 cytokine responses in the supernatant of in vitro-stimulated lymph node cells. In summary, deficiency of the endogenously produced IL-33 and its receptor ST2 does not impact the development of atherosclerosis in ApoE-deficient mice.
authors.affiliation: Division of Rheumatology, University Hospital of Geneva Geneva, Switzerland ; Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Praxedis
authors.initials: P
authors.lastname: Martin
authors.affiliation: Division of Rheumatology, University Hospital of Geneva Geneva, Switzerland ; Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.affiliation: Division of Rheumatology, University Hospital of Geneva Geneva, Switzerland ; Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Division of Rheumatology, University Hospital of Geneva Geneva, Switzerland ; Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Estelle
authors.initials: E
authors.lastname: Woldt
authors.affiliation: Division of Rheumatology, University Hospital of Geneva Geneva, Switzerland ; Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mean
authors.affiliation: Division of Diabetes, Endocrinology and Nutrition Department of Internal Medicine, University Hospital of Geneva Geneva, Switzerland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
authors.affiliation: Inflammation Research Department, Amgen Inc. Seattle, Washington, USA.
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Smith
authors.affiliation: Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland ; Division of Cardiology, University Hospital of Geneva Geneva, Switzerland.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Kwak
authors.affiliation: Division of Rheumatology, University Hospital of Geneva Geneva, Switzerland ; Department of Pathology and Immunology School of Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
keywords: Atherosclerosis; IL-33; ST2; Th1-to-Th2-shift