title: BAFF/BAFF-R involved in antibodies production of rats with collagen-induced arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin.
abstract: BACKGROUND
  Paeoniflorin (Pae) is extracted from the root of paeonia lactiflora which have attracted attention for anti-rheumatic and immune modulating properties.
  
  
  OBJECTIVE
  To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen-induced arthritis (CIA).
  
  
  METHODS
  CIA rats were randomly separated into different groups and treated with Pae (25, 100mg/kg) from day 18 to day 38 after immunization. The effects of Pae on B lymphocytes of CIA rats were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF-R, PI3K, p-Akt and mTOR.
  
  
  RESULTS
  In CIA rats, the levels of anti-CII antibody, IgA, IgG and IgM in serum enhanced, BAFF, BAFF-R, PI3K, p-Akt and mTOR were highly expressed. Pae (100mg/kg) obviously decreased arthritis score, relieved ankle and paw swelling, improved spleen histopathology in CIA rats, decreased the levels of IgA, IgM, IgG and anti-CII antibody, and significantly decreased the expressions of BAFF, BAFF-R, PI3K, p-Akt and mTOR.
  
  
  CONCLUSIONS
  PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats. Pae had therapeutic effects on rats with CIA. These effects might be relative to regulating PI3K/Akt/mTOR signal mediated by BAFF/BAFF-R, and down regulate the antibodies production further.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, 230032 Hefei, China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Li
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Liu
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Song
authors.forename: Qing-Tong
authors.initials: QT
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Wu
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Wen-Di
authors.initials: WD
authors.lastname: Zhao
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D053264:B-Cell Activating Factor / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D001565:Benzoates / Q000302:isolation & purification / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D039821:Monoterpenes; D029596:Paeonia / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D018517:Plant Roots; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D006027:Glycosides
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001565:Benzoates; D001952:Bridged-Ring Compounds; D005960:Glucosides; D039821:Monoterpenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C015423:peoniflorin; D006027:Glycosides; C546845:mTOR protein, rat; C546642:Pik3cd protein, rat; C494920:Akt1 protein, rat; C494923:Akt2 protein, rat; C111490:Akt3 protein, rat