Portal de Periódicos da CAPES

Differential role and tissue specificity of interleukin-1α gene expression in atherogenesis and lipid metabolism

2006; Elsevier BV; Volume: 195; Issue: 1 Linguagem: Inglês

10.1016/j.atherosclerosis.2006.11.026

1879-1484

Yehuda Kamari, Rachel Werman-Venkert, Aviv Shaish, Ariel Werman, Ayelet Harari, Ayelet Gonen, Elena Voronov, Itamar Grosskopf, Yehonatan Sharabi, Ehud Grossman, Yoichiro Iwakura, Charles A. Dinarello, Ron N. Apte, Dror Harats,

Immune Response and Inflammation

We examined the role of IL-1alpha and IL-1beta expressed by bone marrow-derived cells in atherogenesis and lipid metabolism.We first studied the effect of atherogenic diet on wild-type C57BL/6 IL-1alpha or IL-1beta deficient mice. IL-1alpha KO resulted in a comparatively higher total cholesterol levels, compared to WT and IL-1beta KO mice (398+/-10; 266+/-19; 223+/-13 mg/dl, respectively, p<0.001), due to higher non-HDL cholesterol. Nevertheless, aortic sinus lesion area was 56% lower in IL-1alpha KO (p<0.05) and 50% lower in IL-1beta KO (p=0.08), compared to WT mice. Likewise, SAA levels in IL-1alpha KO mice were markedly lower compared to WT and IL-1beta KO mice (31+/-14; 220+/-33 and 106+/-39 microg/ml, respectively, p<0.001). To study the specific role of bone marrow-derived IL-1, irradiated C57BL/6 mice were transplanted with either IL-1+/+, IL-1alpha-/- or IL-1beta-/- bone marrow cells. Despite similar lipoprotein levels, aortic sinus lesion area was 59% lower in IL-1alpha-/- transplanted (p<0.05) compared to IL-1+/+ transplanted mice. Lesion area in IL-1beta-/- was 33% lower than in IL-1+/+ recipient mice, but it was not statistically significant.We demonstrated that early lesion formation is accelerated specifically by bone marrow-derived IL-1alpha. Furthermore, we showed that the expression of IL-1alpha in cells other than the bone marrow plays a significant role in non-HDL cholesterol metabolism.