An Autotaxin/Lysophosphatidic Acid/Interleukin‐6 Amplification Loop Drives Scleroderma Fibrosis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 68; no. 12; pp. 2964 - 2974
• Main Authors: Castelino, Flavia V., Bain, Gretchen, Pace, Veronica A., Black, Katharine E., George, Leaya, Probst, Clemens K., Goulet, Lance, Lafyatis, Robert, Tager, Andrew M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2016
• Subjects: Animals; Benzoates - pharmacology; Bleomycin - toxicity; Case-Control Studies; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Humans; Immunohistochemistry; Interleukin-6 - metabolism; Lysophospholipids - metabolism; Lysophospholipids - pharmacology; Mice; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - drug effects; Phosphoric Diester Hydrolases - metabolism; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; Rodents; Scleroderma, Systemic - metabolism; Scleroderma, Systemic - pathology; Skin - metabolism; Skin - pathology

Objective We previously implicated the lipid mediator lysophosphatidic acid (LPA) as having a role in dermal fibrosis in systemic sclerosis (SSc). The aim of this study was to identify the role of the LPA‐producing enzyme autotaxin (ATX), and to connect the ATX/LPA and interleukin‐6 (IL‐6) pathways...