PMID- 22886597
OWN - NLM
STAT- MEDLINE
DCOM- 20130402
LR  - 20121129
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 64
IP  - 12
DP  - 2012 Dec
TI  - Murine tumor necrosis factor alpha-induced adipose-related protein (tumor necrosis 
      factor alpha-induced protein 9) deficiency leads to arthritis via interleukin-6 
      overproduction with enhanced NF-kappaB, STAT-3 signaling, and dysregulated apoptosis 
      of macrophages.
PG  - 3877-85
LID - 10.1002/art.34666 [doi]
AB  - OBJECTIVE: To elucidate the role of tumor necrosis factor alpha-induced 
      adipose-related protein (TIARP; or tumor necrosis factor alpha-induced protein 9 
      [TNFAIP-9]) in the development and pathogenesis of arthritis. METHODS: We 
      generated TIARP-deficient (TIARP(-/-) ) mice and investigated several organs in 
      aged mice. Peritoneal macrophages were collected and cultured with 
      lipopolysaccharide (LPS) and TNFalpha, and then the production of cytokines and 
      subsequent NF-kappaB signal transduction were analyzed. We also examined the 
      susceptibility of young TIARP(-/-) mice to collagen-induced arthritis (CIA). 
      Draining lymph nodes and splenocytes were isolated and cultured, and serum levels 
      of anti-type II collagen (anti-CII) antibodies, interleukin-6 (IL-6), and TNFalpha on 
      day 60 were measured. We further investigated the effects of anti-IL-6 receptor 
      monoclonal antibody (mAb) on the development of arthritis in TIARP(-/-) mice. 
      IL-6/STAT-3 signaling was also analyzed using TIARP(-/-) macrophages. RESULTS: 
      TIARP(-/-) mice developed spontaneous enthesitis and synovitis, had high serum 
      levels of IL-6, had increased CD11b+ cell counts in the spleen, and showed 
      enhanced LPS- and TNFalpha-induced IL-6 expression in macrophages. Sustained 
      degradation of IkappaBalpha with dysregulated apoptosis was also noted in TIARP(-/-) 
      macrophages. CIA was clearly exacerbated in TIARP(-/-) mice, accompanied by 
      marked neutrophil and macrophage infiltration in joints. The levels of anti-CII 
      antibodies in serum were unchanged, whereas autoreactive Th1 cell and Th17 cell 
      responses were higher in TIARP(-/-) mice. Treatment with anti-IL-6 receptor mAb 
      prevented the development of CIA in TIARP(-/-) mice, and TIARP(-/-) macrophages 
      showed increased IL-6-induced STAT-3 phosphorylation. CONCLUSION: These findings 
      suggest that TIARP acts as a negative regulator of arthritis by suppressing IL-6 
      production, its signaling and TNFalpha-induced NF-kappaB signaling, resulting in enhanced 
      apoptosis in macrophages.
CI  - Copyright (c) 2012 by the American College of Rheumatology.
FAU - Inoue, Asuka
AU  - Inoue A
AD  - Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Matsumoto, Isao
AU  - Matsumoto I
FAU - Tanaka, Yoko
AU  - Tanaka Y
FAU - Umeda, Naoto
AU  - Umeda N
FAU - Tanaka, Yuki
AU  - Tanaka Y
FAU - Mihara, Masahiko
AU  - Mihara M
FAU - Takahashi, Satoru
AU  - Takahashi S
FAU - Sumida, Takayuki
AU  - Sumida T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Tiarp protein, mouse)
SB  - IM
CIN - Arthritis Rheum. 2012 Dec;64(12):3831-4. PMID: 22886549
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Arthritis/*metabolism/pathology
MH  - Arthritis, Experimental/metabolism/pathology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Interleukin-6/*metabolism
MH  - Macrophages, Peritoneal/*pathology
MH  - Male
MH  - Membrane Proteins/*deficiency/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/*physiology
MH  - Th1 Cells/pathology
MH  - Th17 Cells/pathology
EDAT- 2012/08/14 06:00
MHDA- 2013/04/03 06:00
CRDT- 2012/08/14 06:00
PHST- 2012/03/01 00:00 [received]
PHST- 2012/08/02 00:00 [accepted]
PHST- 2012/08/14 06:00 [entrez]
PHST- 2012/08/14 06:00 [pubmed]
PHST- 2013/04/03 06:00 [medline]
AID - 10.1002/art.34666 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2012 Dec;64(12):3877-85. doi: 10.1002/art.34666.