title: [Expression of tumor necrosis factor-alpha signaling adapter proteins in peripheral blood mononuclear cells from patients with systemic lupus erythematosus].
abstract: OBJECTIVE
  To investigate the mRNA expression of the tumor necrosis factor (TNF)-adapter proteins, TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor-interacting protein 1 (RIP-1), and TNF receptor-associated factor-2 (TRAF-2) in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE), and to explore the relationship between the expression of these adaptors and the SLE disease activity.
  
  
  METHODS
  PBMC were isolated from venous blood of 51 SLE patients and 17 healthy subjects. The mRNA expression of TRADD, FADD, RIP-1, TRAF-2, Caspase 3, and interleukin (IL)-1beta were analyzed by quantitative real time RT-PCR. Disease activity was measured using the SLE Disease Activity Index (SLEDAI).
  
  
  RESULTS
  All healthy subjects showed mRNA expressions of TRADD, FADD, RIP-1, and TRAF-2. The mRNA expression levels of TRADD, FADD, RIP-1, and TRAF- in the PBMC from the patients were 0.38, 0.69, 0.59, and 0.55 tomes that from the control subjects (all P < 0.05). The expression levels of these 4 adapters of the SLE patients with the SLEDAI >/= 10 were significantly lower than those of the SLE patients with the SLEDAI < 10 (all P < 0.05). The Caspase3 mRNA expression of the SLE patients was significantly higher than that of the healthy controls (P < 0.01); however, the IL-1beta mRNA expression was not significantly different between the SLE and control subjects. The mRNA expression levels of TRADD, FADD, RIP-1 and TRAF-2 in the PBMC from the SLE patients were all negatively correlated with the SLE activity index with the coefficient correlation of -0.285, -0.280, -0.307, and -0.298 respectively (all P < 0.05).
  
  
  CONCLUSIONS
  The mRNA expression levels of the TNF adapter molecules, such as TRADD, FADD, RIP-1, and TRAF-2, decrease significantly in the PBMC from the SLE patients, and are negatively correlated with the SLE activity index. These abnormalities may participate in the immunopathogenic injury mediated by the aberration TNFalpha signaling pathway in SLE.
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Lang-Jing
authors.initials: LJ
authors.lastname: Zhu
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Chen
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Yu-Lian
authors.initials: YL
authors.lastname: Ji
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Mao
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D012333:RNA, Messenger; D053199:TNF Receptor-Associated Death Domain Protein; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases