Involvement of Interleukin-1 in Lead Nitrate-Induced Hypercholesterolemia in Mice

Access this Article

Author(s)

    • Iwakura Yoichiro
    • Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
    • Degawa Masakuni
    • Department of Molecular Toxicology and Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka

Abstract

Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and cholesterol 7α-hydroxylase (Cyp7a1) are rate-limiting enzymes for cholesterol biosynthesis and catabolism, respectively. Involvement of inflammatory cytokines, particularly interleukin-1 (IL-1), in alterations of <i>HMGR</i> and <i>Cyp7a1</i> gene expression during development of lead nitrate (LN)-induced hypercholesterolemia was examined in IL-1α/β-knockout (IL-1-KO) and wild-type (WT) mice. Lead nitrate treatment of WT mice led to not only a marked downregulation of the <i>Cyp7a1</i> gene at 6—12 h, but also a significant upregulation of the <i>HMGR</i> gene at 12 h. However, such changes were not observed at significant levels in IL-1-KO mice, although a slight, transient downregulation of the <i>Cyp7a1</i> gene and a minimal upregulation of the <i>HMGR</i> gene occurred at 6 h and 24 h, respectively. Consequently, LN treatment led to development of hypercholesterolemia at 24 h in WT mice, but not in IL-1-KO mice. Furthermore, in WT mice, significant LN-mediated increases were observed at 3—6 h in hepatic IL-1 levels, which can modulate gene expression of <i>Cyp7a1</i> and <i>HMGR</i>. These findings indicate that, in mice, LN-mediated increases in hepatic IL-1 levels contribute, at least in part, to altered expressions of <i>Cyp7a1</i> and <i>HMGR</i> genes, and eventually to hypercholesterolemia development.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 35(2), 246-250, 2012

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130001872300
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • NDL Article ID
    023409576
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  J-STAGE 
Page Top