April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Orbital Fibroblasts From Patients With Thyroid-associated Ophthalmopathy Over-express Cd40: Cd154 Hyper-induces Il-6, Il-8 And Mcp-1
C. J. Hwang; N. Afifiyan; D. Sand; V. Naik; J. Said; S. Pollock; B. Chen; R. Phipps; T. Smith; R. Douglas
Author Affiliations & Notes
  • C. J. Hwang
    Orbital & Ophthal Plastic Surg, Jules Stein Eye Inst, UCLA, Los Angeles, California
  • N. Afifiyan
    Molecular Medicine, LA Biomed, Los Angeles, California
  • D. Sand
    Molecular Medicine, LA Biomed, Los Angeles, California
  • V. Naik
    Orbital & Ophthal Plastic Surg, Jules Stein Eye Inst, UCLA, Los Angeles, California
  • J. Said
    Pathology,
    UCLA, Los Angeles, California
  • S. Pollock
    Lung Biology and Disease Program, University of Rochester School of Medicine, Rochester, New York
  • B. Chen
    Molecular Medicine,
    UCLA, Los Angeles, California
  • R. Phipps
    Lung Biology and Disease Program, University of Rochester School of Medicine, Los Angeles, California
  • T. Smith
    Endocrinology,
    UCLA, Los Angeles, California
  • R. Douglas
    Orbital & Ophthal Plastic Surg, Jules Stein Eye Inst, UCLA, Los Angeles, California
  • Footnotes
    Commercial Relationships  C.J. Hwang, None; N. Afifiyan, None; D. Sand, None; V. Naik, None; J. Said, None; S. Pollock, None; B. Chen, None; R. Phipps, None; T. Smith, None; R. Douglas, None.
  • Footnotes
    Support  NIH grants EY008976, EY011708, EY016339, EY014564, DK063121, EY017123, DE011390, ES01247, Research to Prevent Blindness, Heed Ophthalmic Foundation,Los Angeles Biomedical Research Institute, Bell Char
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1537. doi:
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      C. J. Hwang, N. Afifiyan, D. Sand, V. Naik, J. Said, S. Pollock, B. Chen, R. Phipps, T. Smith, R. Douglas; Orbital Fibroblasts From Patients With Thyroid-associated Ophthalmopathy Over-express Cd40: Cd154 Hyper-induces Il-6, Il-8 And Mcp-1. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1537.

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Abstract

Purpose: : Fibroblast diversity represents an emerging concept critical to our understanding of tissue inflammation, repair and remodeling. Orbital fibroblasts heterogeneously display Thy-1 and exhibit unique phenotypic attributes that may explain the susceptibility of the human orbit to thyroid-associated ophthalmopathy (TAO). In the current study we investigate the role of CD40 ligation upon macrophage chemoattractant protein -1 (MCP-1), IL-6 and IL-8 expression in fibroblasts from patients with TAO.

Methods: : Human orbital fibroblasts were cultured from tissues obtained with informed consent from patients with TAO and from patients undergoing surgery for other, non-inflammatory conditions. The fibroblasts were then examined by flow cytometry, microscopy, and cytokine assays.

Results: : We report that orbital fibroblasts from patients with TAO express elevated levels of CD40. Surface CD40 can be further up-regulated by interferon γ (IFN-γ) in both TAO and control fibroblasts. This up-regulation is mediated through Jak2 and can be blocked by dexamethasone and AG490, a powerful and specific inhibitor of the tyrosine kinase. Treatment with CD154, the ligand for CD40, up-regulates the expression of IL-6, IL-8 and MCP-1 in TAO fibroblasts, but fails to do so in control cultures. Thy-1+ fibroblasts displayed higher CD40 levels than do their Thy-1- counterparts and are largely responsible for this cytokine production. IL-1β also induces MCP-1, IL-6 and IL-8 more vigorously in TAO-derived fibroblasts.

Keywords: autoimmune disease • immunohistochemistry • orbit 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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