title: CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway.
abstract: OBJECTIVE
  To explore the influence of chemokine, CXCL16, on the expression of the receptor activator nuclear factor κB ligand (RANKL) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS).
  
  
  METHODS
  The expression of CXCL16/CXCR6 and RANKL in RA or osteoarthritis (OA) patient synovia was examined by Western blot and immunohistochemistry. The serum concentration of CXCL16 and RANKL was measured by enzyme-linked immunosorbent assay (ELISA). RA-FLS were treated with recombinant CXCL16, and RANKL mRNA and protein were measured using PCR, Western blot and ELISA.
  
  
  RESULTS
  The synovial expression of CXCL16, CXCR6, and RANKL was higher in RA patients than in patients with OA. The serum CXCL16 and RANKL levels were higher in RA patients compared with OA patients and healthy controls. CXCL16 correlated with erythrocyte sedimentation rate, C reactive protein, disease activity, serum rheumatoid factor, and RANKL. RA-FLS treated with CXCL16 showed markedly increased expression of RANKL. When STAT3 or p38 activation was blocked by an inhibitor, CXCL16 failed to upregulate RANKL expression. In contrast, inhibiting the Akt or Erk pathway did not achieve the same effect.
  
  
  CONCLUSIONS
  CXCL16 upregulates RANKL expression in RA-FLS and these effects are mainly mediated by the JAK2/STAT3 and p38/MAPK signaling pathways.
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Chang-hong
authors.initials: CH
authors.lastname: Li
authors.affiliation: Department of Clinical Nutrition, First Hospital of Tsinghua Univiersity, Beijing, 100016, People's Republic of China.
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Jin-xia
authors.initials: JX
authors.lastname: Zhao
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Zhong-qiang
authors.initials: ZQ
authors.lastname: Yao
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Deng
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, People's Republic of China. liu-xiangyuan@263.net.
authors.forename: Xiang-yuan
authors.initials: XY
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000097:blood / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053245:RANK Ligand / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D051116:Receptors, Scavenger / Q000097:blood / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D053245:RANK Ligand; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C505688:TNFSF11 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D020928:Mitogen-Activated Protein Kinases
keywords: CXCL16; JAK2/STAT3; RANKL; Rheumatoid arthritis; p38/MAPK