title: Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis.
abstract: OBJECTIVE
  Evaluation of the efficacy of green tea extract (GTE) in regulating chemokine production and chemokine receptor expression in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA).
  
  
  METHODS
  Fibroblasts isolated from human RA synovium were used in the study. Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)alpha/CXCL1 and IL-8/CXCL8 production was measured by ELISA. Western blotting was used to study the phosphorylation of protein kinase C (PKC)delta and c-Jun N-terminal kinases (JNK). Chemokine and chemokine receptor expression was determined by quantitative RT-PCR. The benefit of GTE administration in rat AIA was determined.
  
  
  RESULTS
  GTE (2.5-40 microg/ml) inhibited IL-1beta-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5, GROalpha/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P < 0.05). However, GTE inhibited MCP-1/CCL2 and GROalpha/CXCL1 mRNA synthesis in RA synovial fibroblasts. Furthermore, GTE also inhibited IL-1beta-induced phosphorylation of PKCdelta, the signalling pathway mediating IL-1beta-induced chemokine production. Interestingly, GTE preincubation enhanced constitutive and IL-1beta-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was accompanied by a decrease in MCP-1/CCL2 and GROalpha/CXCL1 levels and enhanced CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered rats.
  
  
  CONCLUSIONS
  Chemokine receptor overexpression with reduced chemokine production by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Department of Veterans Affairs, Ann Arbor, MI, USA.
authors.forename: Hubert
authors.initials: H
authors.lastname: Marotte
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ruth
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Campbell
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
authors.forename: Salahuddin
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013662:Tea; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018925:Chemokines; D010936:Plant Extracts; D019707:Receptors, Chemokine; D013662:Tea