Skip navigation
  • Home
  • Browse
    • Communities
      & Collections
    • Browse Items by:
    • Publication Date
    • Author
    • Title
    • Subject
    • Department
  • Sign on to:
    • My MacSphere
    • Receive email
      updates
    • Edit Profile


McMaster University Home Page
  1. MacSphere
  2. Open Access Dissertations and Theses Community
  3. Open Access Dissertations and Theses
Please use this identifier to cite or link to this item: http://hdl.handle.net/11375/11219
Title: Regulation of macrophage SR-BI by lipoproteins and inflammatory stimuli
Authors: Wang, David Yu Chang
Advisor: Trigatti, Bernardo L.
Igdoura, Suleiman A.
Truant, Ray
Department: Biochemistry
Keywords: Atherosclerosis receptor cholesterol inflammation macrophage lipoprotein;Biochemistry;Biology;Cell Biology;Immunity;Medical Biochemistry;Medical Cell Biology;Medical Molecular Biology;Medical Sciences;Molecular Biology;Biochemistry
Publication Date: Oct-2011
Abstract: <p>In atherosclerotic plaques, macrophages ingest modified LDL and turn to foam cells. Others have shown that SR-BI expression levels inversely correlated with cellular cholesterol levels, and is independent of well characterized cholesterol sensing pathways; SREBP and LXR. Thus the mechanism of regulation of SR-BI is unclear. In this study, we showed that treating macrophage with agents known to increase cellular cholesterol levels, namely acLDL, LDL, MβCD:Cholesterol, resulted in reduction in HMGCoAR mRNA and SR-BI expression levels. In contrast, acLDL did not reduce SR-BI mRNA levels in macrophages from acLDL SR-A KO mice, demonstrating that acLDL mediate suppression of SR-BI was dependent on SR-A. Fucoidan, a known competitive inhibitor of acLDL binding to SR-A, and subsequent degradation, also suppressed SR-BI expression levels. Unlike acLDL, however, fucoidan induced mRNA levels corresponding to the pro-inflammatory genes iNOS and IL-6 mRNA levels, and its effects were not altered by the lack of SR-A. Instead, fucoidan mediated stimulation of iNOS and IL-6 and suppression of SR-BI mRNA levels was prevented by an anti-CD14 blocking antibody, demonstrating that the fucoidan mediated effects were dependent on CD14. Interleukin-15, a pro-inflammatory cytokine that binds to a distinct receptor, also induced iNOS and IL-6 mRNA levels and reduced SR-BI expression, suggesting that inflammatory signaling in general can reduce SR-BI expression levels. Treatment of macrophages with the lipoproteins acLDL, LDL or HDL suppressed the induction of iNOS and IL-6 mRNA by fucoidan or IL-15. Macrophages foam cells in an atherosclerotic plaque may have reduced SR-BI due to exposure with modified LDL or inflammatory cytokines or both in an atherosclerotic plaque. SR-BI expression in macrophages protects against atherosclerosis development. Our data suggests that modified lipoproteins as well as inflammatory stimuli suppress SR-BI expression in macrophages and this may contribute to their pro-apoptotic properties.</p>
URI: http://hdl.handle.net/11375/11219
Identifier: opendissertations/6203
7209
2245848
Appears in Collections:Open Access Dissertations and Theses

Files in This Item:
File SizeFormat 
fulltext.pdf
Open Access
995.53 kBAdobe PDFView/Open
Show full item record Statistics


Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.

Sherman Centre for Digital Scholarship     McMaster University Libraries
©2022 McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8 | 905-525-9140 | Contact Us | Terms of Use & Privacy Policy | Feedback

Report Accessibility Issue