CD34(+) fibrocytes are bone marrow-derived monocyte progenitor cells that 
traffic to sites of tissue injury and repair. They putatively infiltrate the 
orbit in thyroid-associated ophthalmopathy where they appear to transition into 
CD34(+) orbital fibroblasts (OFs) that interact with residential CD34(-) 
fibroblasts. A unique phenotypic attribute of fibrocytes and CD34(+) OFs is 
their expression of the functional thyrotropin receptor (TSHR) and other 
"thyroid-specific" proteins. When activated through TSHR, fibrocytes express a 
number of cytokines and other inflammatory genes. Here we sought to determine 
whether pentraxin-3 (PTX-3), an acute-phase protein involved in inflammation and 
autoimmunity, might be induced by TSH in fibrocytes and OFs. These cells were 
collected from patients with Graves disease and healthy individuals. PTX-3 mRNA 
levels were determined by real-time PCR, protein was determined by ELISA and 
Western blot, and PTX-3 gene promoter activity was assessed with reporter 
assays. PTX-3 expression was induced by TSH in both cell types, regardless of 
the health status of the donor and was a consequence of increased steady-state 
PTX-3 mRNA levels. M22, a TSHR-activating monoclonal antibody, also induced 
PTX-3. The induction could be attenuated by dexamethasone and by IGF-I 
receptor-blocking antibodies, teprotumumab and 1H7. TSH effects were mediated 
through phosphatidylinositol 3-kinase/AKT, mammalian target of 
rapamycin/p70(s6k), Janus tyrosine kinase 2 pathways, and enhanced PTX-3 mRNA 
stability. These findings indicate that PTX-3 is a TSH target gene, the 
expression of which can be induced in fibrocytes and OFs. They suggest that 
PTX-3 might represent a previously unidentified nexus between the thyroid axis 
and the mechanisms involved in tissue remodeling.