title: Phosphatidylserine inhibits inflammatory responses in interleukin-1β-stimulated fibroblast-like synoviocytes and alleviates carrageenan-induced arthritis in rat.
abstract: Recently, phosphatidylserine (PS) has received attention for its anti-inflammatory effect; however, the molecular mechanisms of its action have not been fully understood. Thus, we hypothesized that PS might have antiarthritic and anti-inflammatory effects. To test this hypothesis, the in vitro anti-inflammatory effect of soybean-derived PS was tested on interleukin (IL)-1β-stimulated fibroblast-like synoviocytes from rheumatoid arthritis patients (RA-FLS) by measuring the levels of IL-6, IL-8, prostaglandin E(2), and vascular endothelial growth factor by enzyme-linked immunosorbent assay. The analgesic and antiarthritic activities of PS were investigated in rat models of carrageenan-induced acute paw pain and arthritis. The former was evaluated with a paw pressure test; the latter, by measuring paw volume and weight distribution ratio. In addition, the participation of mitogen-activated protein kinase signaling in the anti-inflammatory and antiarthritic effects of PS was investigated in RA-FLS. Phosphatidylserine inhibited the production of inflammatory mediators IL-6; IL-8; vascular endothelial growth factor; and, in particular, prostaglandin E(2) in IL-1β-stimulated RA-FLS. These effects were associated with abrogation of inhibitor of nuclear factor-κBα phosphorylation and suppression of p38 and c-jun amino terminal kinase but not extracellular signal-regulated kinase 1/2 phosphorylation. In rats, PS also showed a significant inhibitory effect on arthritic and nociceptive symptoms induced by carrageenan. These findings suggest that PS has anti-inflammatory and antiarthritic effects in vitro and in in vivo animal models; thus, PS should be further studied to determine its potential use as either a pharmaceutical or dietary supplement for alleviating arthritic symptoms.
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yeom
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Hahm
authors.forename: Bong-Jun
authors.initials: BJ
authors.lastname: Sur
authors.forename: Jeong-Jun
authors.initials: JJ
authors.lastname: Han
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyung-In
authors.initials: HI
authors.lastname: Yang
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid; D002351:Carrageenan; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology* / Q000627:therapeutic use; D011458:Prostaglandins E / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D010718:Phosphatidylserines; D011458:Prostaglandins E; D042461:Vascular Endothelial Growth Factor A; D002351:Carrageenan; D020928:Mitogen-Activated Protein Kinases