ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1815

STAT3-Mediated Regulation of Mitochondrial Membrane Potential Is Critical for NLRP3 Inflammasome Activation

Jehad H. Edwan1, Raphaela Goldbach-Mansky2 and Robert A. Colbert3, 1NIAMS NIH, Bethesda, MD, 2NIAMS, NIH Building 10 Room 6D47B, Bethesda, MD, 3NIAMS/NIH, Bethesda, MD

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: IL-1/IL-18, inflammasome activation, Inflammation, innate immunity and monocytes

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Innate Immunity and Rheumatic Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: Self-activating mutations in NLRP3 cause a spectrum of autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS). NLRP3 is a key component of a multiprotein complex known as the inflammasome that mediates the maturation of the proinflammatory cytokine IL-1beta, and can induce rapid cell death in a process known as pyronecrosis. Although several models for inflammasome activation have been proposed the precise molecular mechanism, as well as the role of NRLP3 mutations, remains to be elucidated. Emerging evidence suggests that mitochondria are involved in inflammasome activation. STAT3 associates with the mitochondrial inner membrane in a GRIM-19 dependent manner and has been implicated in regulating cellular respiration. Here we asked whether regulation of mitochondrial membrane potential plays a role in NLRP3 inflammasome activation.
Methods: We used whole blood cells from NOMID patients and healthy controls, THP-1 cells with STAT3, NLRP3, GRIM-19, or OSCP expression knocked down, and monocytes derived from NLRP3-deficient mice. Cells were stimulated with LPS in the presence of inhibitors of STAT3, followed by ATP. Cell supernatants were collected and incubated with IL-1beta-capturing beads. Cells were fixed and permeabilized. Then beads were added back to cells, and the mixture of cells with beads was stained with anti-IL-1beta, CD14, and CD16 antibodies and then evaluated by flow cytometry. LPS stimulated cells were also evaluated using immunofluorescence and western blot analysis.
Results: By flow analysis we provide evidence that inhibition of STAT3 function in NOMID and healthy control monocytes, as well as knockdown of STAT3 in THP-1 cells, results in a significant decrease in inflammasome activation. Using confocal microscopy to visualize pyronecrosis, we provide evidence that this process is NLRP3 dependent.  Knockdown of GRIM-19 in THP-1 cells also inhibited NLRP3 activation, suggesting a requirement for mitochondrial STAT3. Enhancement of the mitochondrial membrane potential in STAT3 knockdown cells bypassed the effect of STAT3 knockdown, and reconstituted inflammasome activation, whereas knockdown of OSCP significantly reduced inflammasome activation.
Conclusion:
These data suggest a previously unrecognized role for STAT3 in regulating mitochondrial membrane potential, which can regulate NLRP3 inflammasome activation. These results point toward mitochondrial STAT3 as a novel therapeutic target for NOMID and other NLRP3-mediated inflammatory diseases.


Disclosure:

J. H. Edwan,
None;

R. Goldbach-Mansky,
None;

R. A. Colbert,
None.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/stat3-mediated-regulation-of-mitochondrial-membrane-potential-is-critical-for-nlrp3-inflammasome-activation/

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 »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology