CD34- Orbital Fibroblasts From Patients With Thyroid-Associated Ophthalmopathy Modulate TNF-α Expression in CD34+ Fibroblasts and Fibrocytes

Investigative Ophthalmology & Visual Science
Yan LuTerry J Smith

Abstract

Orbital fibroblasts from patients with Graves' disease (GD-OF) express many different cytokines when treated with bovine thyrotropin (bTSH). The present study aimed to determine why TNF-α cannot be induced by bTSH in GD-OF. Fibrocytes and GD-OFs were cultivated from donors who were patients in a busy academic medical center practice. Real-time PCR, Western blot analysis, reporter gene assays, cell transfections, mRNA stability assays, ELISA, and flow cytometry were performed. We found that bTSH induces TNF-α dramatically in fibrocytes but is undetectable in GD-OF. The induction in fibrocytes is a consequence of increased TNF-α gene promoter activity and is independent of ongoing protein synthesis. It could be attenuated by dexamethasone and the IGF-1 receptor inhibiting antibody, teprotumumab. When separated into pure CD34+ OF and CD34- OF subsets, TNF-α mRNA became highly inducible by bTSH in CD34+ OF but remained undetectable in CD34- OF. Conditioned medium from CD34- OF inhibited induction of TNF-α in fibrocytes. Our data indicate that CD34- OF appear to release a soluble(s) factor that downregulates expression and induction by bTSH of TNF-α in fibrocytes and their derivative CD34+ OF. We proffer that CD34- OF produce an uni...Continue Reading

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Citations

Nov 18, 2018·The Journal of Clinical Endocrinology and Metabolism·Terry J Smith
Jan 1, 2020·Nature Reviews. Endocrinology·Peter N TaylorMarian Ludgate
Jan 5, 2021·Frontiers in Endocrinology·Terry J Smith
Oct 29, 2020·Taiwan Journal of Ophthalmology·Yazhuo HuangHuifang Zhou
Mar 12, 2021·The Journal of Clinical Endocrinology and Metabolism·Lu ShiHuasheng Yang
Aug 22, 2021·Journal of Endocrinological Investigation·E J Neag, T J Smith
Jan 29, 2022·Proceedings of the National Academy of Sciences of the United States of America·Richard J Bucala

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Methods Mentioned

BETA
fluorescence activated cell sorter
protein assay
Assay
ELISA
Transfections
PCR
transfection
flow cytometry

Software Mentioned

Image Pro Plus

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