Novel aspects of orbital fibroblast pathology.
Orbital fibroblasts exhibit a unique phenotype including exaggerated responses to proinflammatory cytokines. We hypothesize that the unusual susceptability of these fibroblasts to molecular cues underlies the involvement of the orbit in Graves' ophthalmopathy. A number of attributes of orbital fibroblasts are reviewed in this article. In addition, we have found IgG circulating in patients with Graves' disease that binds and activates the insulin-like growth factor-1 receptor displayed on fibroblasts from many anatomic regions. Activation of this receptor leads to the expression of T-cell chemoattractants. Thus, fibroblast activation, and the resulting T-cell trafficking to connective tissue in Graves' disease may be systemic. The consequences of lymphocyte-derived cytokine action may differ vastly in the orbit and other tissues manifesting clinically obvious disease.
Smith
T J
TJ
Division of Molecular Medicine, Department of Medicine, Harbor-UCLA Medical Center, Torrance 90502, USA. tjsmith@ucla.edu
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology*; D006111:Graves Disease / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D009915:Orbit / Q000473:pathology*; D010641:Phenotype
D019013:CD40 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D023201:CD40 Ligand; D006820:Hyaluronic Acid; D015232:Dinoprostone