ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 631

Type I IFN Regulation Of IL-10 Is Detrimental To Endothelial Cell Differentiation and May Enhance Cardiovascular Risk In Systemic Lupus Erythematosus

J. Michelle Kahlenberg1, Alyssa Cates2, Victoria Holden3, Carolyne K. Smith4 and Mariana J. Kaplan5, 1Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, 2Internal Medicine, Rheumatology, University of Michigan, Ann Arbor, MI, 3Pathology, University of Michigan, Ann Arbor, MI, 4Rheumatology and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI, 5Systemic Autoimmunity Branch, National Institutes of Health/NIAMS, Bethesda, MD

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Cardiovascular disease, endothelial cells, interferons and interleukins (IL)

  • Tweet
  • Email
  • Print
Session Information

Session Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Mechanisms and Biomarkers

Session Type: Abstract Submissions (ACR)

Background/Purpose: Systemic Lupus Erythematosus (SLE) is a heterogeneous disease resulting in organ damage and an elevated risk of cardiovascular disease (CVD).  Previous reports have suggested that type-I interferon (IFN)-mediated repression of IL-1β and activation of IL-18 are important pathways leading to endothelial dysfunction and CVD in lupus patients.  While typically viewed as anti-inflammatory, Interleukin-10 (IL-10) levels are elevated in SLE patients, where they may play pathogenic roles related to immune activation of B cell responses.  Furthermore, IL-10 induces transcriptional repression of IL-1β synthesis.  This study explores whether IL-10 has a detrimental effect on endothelial progenitor cell (EPC) differentiation and function and whether it may play a role in type I IFN-mediated repression of IL-1β in SLE with secondary detrimental effects on neoangiogenesis.   

Methods: Human and murine control and lupus EPCs were induced to differentiate into mature endothelial cells (ECs) in the presence or absence of graded concentrations of recombinant  IL-10 or a neutralizing Ab to this cytokine. IL-10 deficient mice were used to assess the role of this cytokine in type I IFN-mediated inhibition of neoangiogenesis using an in vivo Matrigel plug assay.

Results: In murine EPC/CAC cultures, the inhibitory effects of IFN-α on EPC/CAC differentiation were abrogated using an anti-IL-10 neutralizing antibody or cultures from IL-10 -/- mice.  Further, the inhibitory effects of IFN-α on neoangiogensis in vivo were abrogated in IL-10 -/- mice.  In human EPC cultures, anti-IL-10 neutralizing antibodies did not significantly impact the differentiation of control cells, but improved the differentiation of SLE EPCs into mature ECs.  Conversely, addition of recombinant IL-10 was detrimental to EPC growth and differentiation and this was enhanced by type I IFNs in both control and SLE cultures.  Upregulation of IL-10 was detected following type I IFN treatment of early EPC cultures , while both  recombinant IL-10 and IFN-α resulted in enhanced repression of IL-1β in these cells.

Conclusion: These results indicate that IL-10 is detrimental to vasculogenesis and is an important intermediary in the IFN-α-mediated repression of proangiogenic IL-1β previously observed in these cells.  As type I IFNs induce IL-10 synthesis, these results indicate that elevated levels of IL-10 in SLE patients may be associated with cardiovascular risk .


Disclosure:

J. M. Kahlenberg,
None;

A. Cates,
None;

V. Holden,
None;

C. K. Smith,
None;

M. J. Kaplan,
None.

  • Tweet
  • Email
  • Print

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/type-i-ifn-regulation-of-il-10-is-detrimental-to-endothelial-cell-differentiation-and-may-enhance-cardiovascular-risk-in-systemic-lupus-erythematosus/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies