Regulation of IL-1 Receptor Antagonist by TSH in Fibrocytes and Orbital Fibroblasts

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2014 Jan 23

PMID 24446657

Citations 16

Authors

Bin Li

Terry J Smith

Affiliations

Soon will be listed here.

Abstract

Context: The IL-1 family plays important roles in normal physiology and mediates inflammation. The actions of IL-1 are modulated by multiple IL-1 receptor antagonists (IL-1RA), including intracellular and secreted forms. IL-1 has been implicated in autoimmunity, such as that occurring in Graves' disease (GD) and its inflammatory orbital manifestation, thyroid-associated ophthalmopathy (TAO). We have previously reported that CD34(+) fibrocytes, monocyte-lineage bone marrow-derived cells, express functional TSH receptor, the central antigen in GD. When activated by TSH, they produce IL-6, IL-8, and TNF-α. Moreover, they infiltrate the orbit in TAO in which they transition into CD34(+) fibroblasts and comprise a population of orbital fibroblasts (OFs). Little is known currently about any relationship between TSH, TSH receptor, and the IL-1 pathway.

Objective: The objective of the study was to determine whether TSH regulates IL-1RA in fibrocytes and OFs.

Design/setting/participants: Fibrocytes and OFs were collected and analyzed from healthy individuals and those with GD in an academic clinical practice.

Main Outcome Measures: Real-time PCR, Western blot analysis, reporter gene assays, and cell transfections were performed.

Results: TSH induces the expression of IL-1RA in fibrocytes and GD-OFs. The patterns of induction diverge quantitatively and qualitatively in the two cell types. This results from relatively small effects on gene transcription-related events but a greater influence on secreted IL-1RA and intracellular IL-1RA mRNA stabilities. These actions of TSH are dependent on the intermediate induction of IL-1α and IL-1β.

Conclusions: Our findings for the first time directly link activities of the TSH and IL-1 pathways. Furthermore, they identify novel molecular interactions that could be targeted as therapy for TAO.

Citing Articles

Cytokines in Thyroid-Associated Ophthalmopathy.

Zhang P, Zhu H J Immunol Res. 2022; 2022:2528046.

PMID: 36419958 PMC: 9678454. DOI: 10.1155/2022/2528046.

Fibulin-1: a novel biomarker for predicting disease activity of the thyroid-associated ophthalmopathy.

Hu H, Liang L, Zheng X, Jiang X, Fu Z, Liu C Eye (Lond). 2022; 37(11):2216-2219.

PMID: 36418908 PMC: 10366185. DOI: 10.1038/s41433-022-02318-6.

Potential Therapeutic Activity of Berberine in Thyroid-Associated Ophthalmopathy: Inhibitory Effects on Tissue Remodeling in Orbital Fibroblasts.

Diao J, Chen X, Mou P, Ma X, Wei R Invest Ophthalmol Vis Sci. 2022; 63(10):6.

PMID: 36094643 PMC: 9482321. DOI: 10.1167/iovs.63.10.6.

Teprotumumab Divergently Alters Fibrocyte Gene Expression: Implications for Thyroid-associated Ophthalmopathy.

Fernando R, Smith T J Clin Endocrinol Metab. 2022; 107(10):e4037-e4047.

PMID: 35809263 PMC: 9516078. DOI: 10.1210/clinem/dgac415.

2021 update on thyroid-associated ophthalmopathy.

Neag E, Smith T J Endocrinol Invest. 2021; 45(2):235-259.

PMID: 34417736 PMC: 9455782. DOI: 10.1007/s40618-021-01663-9.

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