TY - JOUR
T1 - Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis
AU - Nikitopoulou, Ioanna
AU - Oikonomou, Nikos
AU - Karouzakis, Emmanuel
AU - Sevastou, Ioanna
AU - Nikolaidou-Katsaridou, Nefeli
AU - Zhao, Zhenwen
AU - Mersinias, Vassilis
AU - Armaka, Maria
AU - Xu, Yan
AU - Masu, Masayuki
AU - Mills, Gordon B.
AU - Gay, Steffen
AU - Kollias, George
AU - Aidinis, Vassilis
PY - 2012/5/7
Y1 - 2012/5/7
N2 - Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes a substantial socioeconomic burden. Under the influence of the proinflammatory milieu, synovial fibroblasts (SFs), the main effector cells in disease pathogenesis, become activated and hyperplastic, releasing proinflammatory factors and tissueremodeling enzymes. This study shows that activated arthritic SFs from human patients and animal models express significant quantities of autotaxin (ATX; ENPP2), a lysophospholipase D that catalyzes the conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX expression from SFs was induced by TNF, and LPA induced SF activation and effector functions in synergy with TNF. Conditional genetic ablation of ATX in mesenchymal cells, including SFs, resulted in disease attenuation in animal models of arthritis, establishing the ATX/LPA axis as a novel player in chronic inflammation and the pathogenesis of arthritis and a promising therapeutic target.
AB - Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes a substantial socioeconomic burden. Under the influence of the proinflammatory milieu, synovial fibroblasts (SFs), the main effector cells in disease pathogenesis, become activated and hyperplastic, releasing proinflammatory factors and tissueremodeling enzymes. This study shows that activated arthritic SFs from human patients and animal models express significant quantities of autotaxin (ATX; ENPP2), a lysophospholipase D that catalyzes the conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX expression from SFs was induced by TNF, and LPA induced SF activation and effector functions in synergy with TNF. Conditional genetic ablation of ATX in mesenchymal cells, including SFs, resulted in disease attenuation in animal models of arthritis, establishing the ATX/LPA axis as a novel player in chronic inflammation and the pathogenesis of arthritis and a promising therapeutic target.
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U2 - 10.1084/jem.20112012
DO - 10.1084/jem.20112012
M3 - Article
C2 - 22493518
AN - SCOPUS:84863793425
SN - 0022-1007
VL - 209
SP - 925
EP - 933
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -