NDLI: Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-κB.

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Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-κB.

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Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-κB.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Raychaudhuri, Nupur Smith, Terry J. Lu, Ying Papageorgiou, Konstantinos I. Charara, Laya K. Atkins, Stephen J. Mester, Tünde Douglas, Raymond S. Gillespie, Erin F.
Description	Country affiliation: United States Author Affiliation: Gillespie EF ( Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Kellogg Eye Center, Ann Arbor, Michigan 48105, USA.)
Abstract	PURPOSE: CD40-CD40 ligand (CD40L) interactions appear to play pathogenic roles in autoimmune disease. Here we quantify CD40 expression on fibrocytes, circulating, and bone marrow-derived progenitor cells. The functional consequences of CD40 ligation are determined since these may promote tissue remodeling linked with thyroid-associated ophthalmopathy (TAO). METHODS: CD40 levels on cultivated fibrocytes and orbital fibroblasts (GOFB) from patients with Graves' disease (GD), as well as fibrocyte abundance, were determined by flow cytometry. CD40 mRNA expression was evaluated by real-time PCR, whereas response to CD40 ligation was measured by Luminex and RT-PCR. Protein kinase B (Akt) and nuclear factor (NF)-kappa B (NF-κB) signaling were determined by Western blot and immunofluorescence. RESULTS: Basal CD40 expression on fibrocytes is greater than that on GOFB. IFN-Î³ upregulates CD40 in both cell types and its actions are mediated at the pretranslational level. Fibrocytes produce high levels of cytokines, including interleukin-6 (IL-6), TNF- , IL-8, MCP-1, and RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted) in response to CD40L. IL-6 induction results from an increase in steady state IL-6 mRNA, and is mediated through Akt and NF-κB activation. Circulating CD40(+)CD45(+)Col1(+) fibrocytes are far more frequent in vivo in donors with TAO compared with healthy subjects. CONCLUSIONS: Particularly high levels of functional CD40 are displayed by fibrocytes. CD40L-provoked signaling results in the production of several cytokines. Among these, IL-6 expression is mediated through Akt and NF-κB pathways. The frequency of circulating CD40(+) fibrocytes is markedly increased in patients with TAO, suggesting that this receptor might represent a therapeutic target for TAO.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.12-9861
Journal	Investigative Opthalmology & Visual Science
Issue Number	12
Volume Number	53
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2012-11-21
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd40 Genetics Gene Expression Regulation Graves Ophthalmopathy Interleukin-6 Nf-kappa B Proto-oncogene Proteins C-akt Rna, Messenger Biosynthesis Blotting, Western Cells, Cultured Fibroblasts Metabolism Pathology Flow Cytometry Microscopy, Fluorescence Orbit Real-time Polymerase Chain Reaction Signal Transduction Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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