title: Synovial fibroblasts integrate inflammatory and neuroendocrine stimuli to drive rheumatoid arthritis.
abstract: Rheumatoid arthritis is a chronic inflammatory disease that is characterized by pannus tissue consisting of synovial fibroblasts (SF), macrophages and lymphocytes. The inflammatory milieu in the joint activates resident SF and transforms them in a tumor-like phenotype. These changes manifest in resistance to Fas-induced apoptosis and production of cytokines, chemokines and matrix metalloproteinases. By alterations in DNA methylation, SF retain their transformed phenotype even in the absence of pro-inflammatory stimuli and are able to spread arthritis to unaffected joints. Furthermore, SF integrate neuroendocrine input to modulate inflammation since they possess receptors for several neurotransmitters (e.g., dopamine, norepinephrine and glutamate). Until now, no specific therapy targeting SF is available; however, reprogramming them to a regulatory phenotype might limit joint destruction and cartilage degradation.
authors.affiliation: a Department of Internal Medicine I, Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, University Hospital of Regensburg, D-93042 Regensburg, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Lowin
authors.affiliation: a Department of Internal Medicine I, Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, University Hospital of Regensburg, D-93042 Regensburg, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D004703:Endocrine System / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D009420:Nervous System / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha
keywords: TNF; catecholamines; cytokines; sympathetic nervous system; synovial fibroblasts