title: Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNFalpha) plays a pivotal role in rheumatoid arthritis (RA); however, the mechanism of action of TNFalpha antagonists in RA is poorly defined. Immunization of DBA/1 mice with glucose-6-phosphate isomerase (GPI) induces severe acute arthritis. This arthritis can be controlled by TNFalpha antagonists, suggesting similar etiology to RA. In this study, we explored TNFalpha-related mechanisms of arthritis.
  
  
  METHODS
  First, we performed GeneChip analysis using splenocytes of mice with GPI-induced arthritis. Expression of TNFalpha-induced adipose-related protein (TIARP) mRNA and protein in spleens, joints and lymph nodes was evaluated, and fluctuation of TIARP mRNA was analyzed after administration of anti-TNFalpha monoclonal antibody (mAb). Localization of TIARP in spleen and joints was also explored. Six-transmembrane epithelial antigen of the prostate (STEAP) families of proteins, the human ortholog of TIARP gene, were also evaluated in human peripheral blood mononucleocytes and synovium.
  
  
  RESULTS
  Among the arrayed TNFalpha-related genes, the expression of TIARP mRNA was the highest (more than 20 times the control). TIARP mRNA was detected specifically in joints and spleens of arthritic mice, and their levels in the synovia correlated with severity of joint swelling. Treatment with anti-TNF mAb significantly reduced TIARP mRNA expression in splenocytes. Among the splenocytes, CD11b+ cells were the main source of TIARP mRNA. Immunohistochemistry showed that TIARP protein was mainly localized in hyperplastic synovium. Among the STEAP family of proteins, STEAP4 was highly upregulated in joints of patients with RA and especially co-localized with CD68+ macrophages.
  
  
  CONCLUSIONS
  The results shed light on the new mechanism of action of TNFalpha antagonists in autoimmune arthritis, suggesting that TIARP plays an important role in inflammatory arthritis, through the regulation of inflammatory cytokines.
authors: Division of Clinical Immunology, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan. c0830413@md.tsukuba.ac.jp
authors: Asuka
authors: A
authors: Inoue
authors: Isao
authors: I
authors: Matsumoto
authors: Yoko
authors: Y
authors: Tanaka
authors: Keiichi
authors: K
authors: Iwanami
authors: Akihiro
authors: A
authors: Kanamori
authors: Naoyuki
authors: N
authors: Ochiai
authors: Daisuke
authors: D
authors: Goto
authors: Satoshi
authors: S
authors: Ito
authors: Takayuki
authors: T
authors: Sumida
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D018845:CD11 Antigens / Q000276:immunology; D015870:Gene Expression; D005786:Gene Expression Regulation; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis; D010088:Oxidoreductases / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018845:CD11 Antigens; D005956:Glucose-6-Phosphate Isomerase; D008565:Membrane Proteins; D010088:Oxidoreductases; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C436323:Tiarp protein, mouse; C503310:STEAP4 protein, human