TSH and CD40L Stimulate Interleukin-12 Expression in Fibrocytes: Implications for pathogenesis of Thyroid Associated Ophthalmopathy.

TSH and CD40L Stimulate Interleukin-12 Expression in Fibrocytes: Implications for pathogenesis of Thyroid Associated Ophthalmopathy.

Thyroid. 2016 Sep 9;

Authors: Wu T, Mester T, Gupta S, Sun F, Smith TJ, Douglas R

Abstract
BACKGROUND: Increased numbers of bone marrow-derived progenitor cells, known as fibrocytes populate the peripheral circulation, orbit, and thyroid of patients with Graves' disease (GD). These cells have been implicated in the development of thyroid-associated ophthalmopathy (TAO). They can differentiate into myofibroblasts or adipocytes, produce inflammatory cytokines, and remodel tissue. We sought to determine whether thyroid-stimulating hormone (TSH) and CD40 ligand (CD40L) implicated in the pathogenesis of GD, induce interleukin-12 (IL-12) in human fibrocytes.
MATERIALS AND METHODS: IL-12 protein concentrations and mRNA levels were measured by Luminex and real-time polymerase chain reaction, respectively. Flow cytometry assessed intracellular IL-12 concentrations. Vector containing IL-12p40 promoter was transfected into cultured fibrocytes and promoter activity was monitored using luciferase assay.
RESULTS: TSH and CD40L stimulated intracellular IL-12 protein accumulation in peripheral blood fibrocytes. Inhibiting Akt and nuclear factor-κB (NF-κB) activity diminished IL-12 expression in fibrocytes while TSH did not induce promoter activity. TSH-mediated IL-12 production required de novo-synthesized proteins and augmented IL-12 mRNA stability. IL-12 production mediated by CD40L required tumor necrosis factor receptor-associated factor 6 (TRAF6).
CONCLUSION: TSH and CD40L induce IL-12 expression in fibrocytes, and Akt and NF-κB mediate this activity. Given the importance of IL-12 in immune function, its production by fibrocytes may promote an inflammatory immune response and tissue remodeling in TAO.

PMID: 27612658 [PubMed - as supplied by publisher]

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