Interleukin-1β attenuates β-very low-density lipoprotein uptake and its receptor expression in vascular smooth muscle cells

Masafumi Takahashi, Sadao Takahashi, Chihiro Suzuki, Lijing Jia, Hajime Morimoto, Hirohiko Ise, Tadao Iwasaki, Hiroaki Hattori, Jinya Suzuki, Isamu Miyamori, Eiji Kobayashi, Uichi Ikeda

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Abstract

The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor gene family with distinct tissue distribution and function. VLDL receptors are also expressed in vascular smooth muscle cells (VSMCs) and have been shown to be upregulated in atherosclerotic lesions. In the present study, we examined the effects of interleukin-1β (IL-1β) on the uptake of βVLDL and its receptor expression in rat VSMCs. IL-1β downregulated expression of the VLDL receptor in a time and dose-dependent manner as shown by Western blotting, Northern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Treatment with IL-1β significantly reduced the uptake of β-VLDL but not LDL in VSMCs. Use of specific pharmacologic inhibitors indicated that the tyrosine kinase inhibitors, herbimycin A and geldanamycin, completely reversed IL-1β-induced downregulation of the VLDL receptor expression. Another tyrosine kinase inhibitor, genistein, the protein kinase C inhibitors, GF109203X and H7, the mitogen-activated protein (MAP) kinase inhibitors (MEK inhibitor PD098059 for [MEK] and SB203580 for p38-MAP kinase), and the protein kinase A inhibitor, KT5270 all had no effect on receptor expression. In addition, the c-Src specific inhibitor PP2 or adenoviral-mediated gene transfer of kinase inactive (KI)-c-Src failed to reverse IL-1β-induced downregulation of VLDL receptor expression. These results indicate that IL-1β attenuates uptake of VLDL through downregulation of its receptor in VSMCs, and that this downregulation is mediated through a benzoquinone ansamycin-dependent but c-Src-independent pathway.

Original languageEnglish
Pages (from-to)637-646
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 2005

Fingerprint

VLDL Lipoproteins
Interleukin-1
Vascular Smooth Muscle
Smooth Muscle Myocytes
Down-Regulation
Mitogen-Activated Protein Kinase Kinases
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Rifabutin
Protein C Inhibitor
Genistein
LDL Receptors
p38 Mitogen-Activated Protein Kinases
Tissue Distribution
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
Reverse Transcriptase Polymerase Chain Reaction
LDL Lipoproteins
Northern Blotting
Protein Kinase C

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Interleukin-1β attenuates β-very low-density lipoprotein uptake and its receptor expression in vascular smooth muscle cells. / Takahashi, Masafumi; Takahashi, Sadao; Suzuki, Chihiro; Jia, Lijing; Morimoto, Hajime; Ise, Hirohiko; Iwasaki, Tadao; Hattori, Hiroaki; Suzuki, Jinya; Miyamori, Isamu; Kobayashi, Eiji; Ikeda, Uichi.

In: Journal of Molecular and Cellular Cardiology, Vol. 38, No. 4, 04.2005, p. 637-646.

Research output: Contribution to journalArticle

Takahashi, M, Takahashi, S, Suzuki, C, Jia, L, Morimoto, H, Ise, H, Iwasaki, T, Hattori, H, Suzuki, J, Miyamori, I, Kobayashi, E & Ikeda, U 2005, 'Interleukin-1β attenuates β-very low-density lipoprotein uptake and its receptor expression in vascular smooth muscle cells', Journal of Molecular and Cellular Cardiology, vol. 38, no. 4, pp. 637-646. https://doi.org/10.1016/j.yjmcc.2005.02.006
Takahashi, Masafumi ; Takahashi, Sadao ; Suzuki, Chihiro ; Jia, Lijing ; Morimoto, Hajime ; Ise, Hirohiko ; Iwasaki, Tadao ; Hattori, Hiroaki ; Suzuki, Jinya ; Miyamori, Isamu ; Kobayashi, Eiji ; Ikeda, Uichi. / Interleukin-1β attenuates β-very low-density lipoprotein uptake and its receptor expression in vascular smooth muscle cells. In: Journal of Molecular and Cellular Cardiology. 2005 ; Vol. 38, No. 4. pp. 637-646.
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AU - Morimoto, Hajime

AU - Ise, Hirohiko

AU - Iwasaki, Tadao

AU - Hattori, Hiroaki

AU - Suzuki, Jinya

AU - Miyamori, Isamu

AU - Kobayashi, Eiji

AU - Ikeda, Uichi

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AB - The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor gene family with distinct tissue distribution and function. VLDL receptors are also expressed in vascular smooth muscle cells (VSMCs) and have been shown to be upregulated in atherosclerotic lesions. In the present study, we examined the effects of interleukin-1β (IL-1β) on the uptake of βVLDL and its receptor expression in rat VSMCs. IL-1β downregulated expression of the VLDL receptor in a time and dose-dependent manner as shown by Western blotting, Northern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Treatment with IL-1β significantly reduced the uptake of β-VLDL but not LDL in VSMCs. Use of specific pharmacologic inhibitors indicated that the tyrosine kinase inhibitors, herbimycin A and geldanamycin, completely reversed IL-1β-induced downregulation of the VLDL receptor expression. Another tyrosine kinase inhibitor, genistein, the protein kinase C inhibitors, GF109203X and H7, the mitogen-activated protein (MAP) kinase inhibitors (MEK inhibitor PD098059 for [MEK] and SB203580 for p38-MAP kinase), and the protein kinase A inhibitor, KT5270 all had no effect on receptor expression. In addition, the c-Src specific inhibitor PP2 or adenoviral-mediated gene transfer of kinase inactive (KI)-c-Src failed to reverse IL-1β-induced downregulation of VLDL receptor expression. These results indicate that IL-1β attenuates uptake of VLDL through downregulation of its receptor in VSMCs, and that this downregulation is mediated through a benzoquinone ansamycin-dependent but c-Src-independent pathway.

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