Abstract
Purpose: :
Orbital fibroblasts are key players in the pathophysiology of Graves Ophthalmopathy (GO). It has been proposed that orbital fibroblasts (OF) differ from fibroblasts from other anatomical regions and that they respond differently to stimuli than fibroblasts from other body parts. Furthermore, OF from GO patients might display intrinsic differences to OF from healthy controls and respond in a different way to stimuli. However, the data supporting these suggestions are merely based on studies determining only few outcome parameters. As the existence of intrinsic differences between OF and fibroblasts from other anatomical regions or between OF from GO or non-GO orbital tissue could be an important determinant in the occurrence of GO, we performed a comprehensive study in which we compared the production of 120 cytokines by OF and dermal fibroblasts, either unstimulated or upon PDGF-BB stimulation (which is an important factor in GO pathology).
Methods: :
OF from GO patients and healthy controls or dermal fibroblasts were stimulated with or without PDGF-BB. Supernatants were subjected to the Quantibody Human Cytokine Antibody Array 2000 (RayBiotech), which comprises 120 cytokines, chemokines and growth factors.
Results: :
OF clustered differently from dermal fibroblasts based on their protein production profile. Furthermore, upon stimulation with PDGF-BB, OF still produced a distinct cluster of proteins which was clearly different from that produced by dermal fibroblasts. No differences were observed between OF from GO patients or healthy controls.
Conclusions: :
We show that OF produce a unique cluster of proteins compared to dermal fibroblasts. This intrinsic difference was maintained upon PDGF-BB stimulation, which underlines the unique properties of orbital fibroblasts and might explain the orbital localization of GO. No differences in protein profiles were found between OF from GO patients or healthy controls. Therefore, the actual occurrence of GO seems to be mainly driven by mediators locally present in orbital tissue of GO patients.
Keywords: orbit • inflammation • proteomics