PMID- 31231373
OWN - NLM
STAT- MEDLINE
DCOM- 20200720
LR  - 20200720
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Downregulation of Transcription Factor T-Bet as a Protective Strategy in 
      Monosodium Urate-Induced Gouty Inflammation.
PG  - 1199
LID - 10.3389/fimmu.2019.01199 [doi]
LID - 1199
AB  - Gout is sterile joint inflammation triggered by the damaging effects of 
      monosodium urate (MSU) crystals accumulation. Previous studies suggest 
      transcription factor T-bet plays an important role in inflammatory arthritis. 
      Notably, mice lacking T-bet markedly reduced joint inflammation of rheumatoid 
      arthritis models, however, the involvement of T-bet in gouty inflammation has yet 
      to be clarified. Here, we took advantage of T-bet knockout (KO) mice to 
      investigate the role of T-bet in the pathogenesis of MSU-induced gout 
      inflammation. T-bet KO and wild type (WT) mice were used for models of acute 
      inflammation induced with MSU crystals, including footpad, air pouch and 
      peritonitis models. Inflammatory cytokines and phagocytosis were detected in 
      bone-marrow-derived macrophages (BMDMs) from T-bet KO and WT mice treated with 
      MSU crystals in vitro. In addition, T-bet expression in peripheral blood 
      mononuclear cells (PBMCs) from gout patients was measured, as well as plasma 
      inflammatory cytokines. We found that the levels of interleukin (IL)-17, IL-23, 
      and interferon-gamma were reduced, but tumor necrosis factor-alpha was not, in BMDMs from 
      T-bet KO compared with WT mice after MSU challenge in vitro, as well as MSU 
      phagocytosis. In comparison with WT mice in vivo, the swelling index of T-bet KO 
      mice was significantly decreased in the footpad model. T-bet deficiency also 
      dramatically relieved MSU-induced inflammatory cell infiltration in peritonitis 
      and air pouch models in vivo, and as well as the IL-1beta levels of air pouch lavage 
      fluid (APLF). In addition, plasma IL-17 and IL-23 levels were elevated in acute 
      gout, whereas protein levels of T-bet were downregulated in PBMCs from acute gout 
      patients and intercritical gout treated with MSU crystals in vitro as well. 
      Transcription factor T-bet deficiency protects against MSU-induced gouty 
      inflammation, suggesting that downregulation of T-bet could be a protective 
      strategy and contribute to spontaneous remission of inflammation in acute gout.
FAU - Yang, Qi-Bin
AU  - Yang QB
AD  - Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan 
      Medical College, Nanchong, China.
FAU - He, Yong-Long
AU  - He YL
AD  - Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan 
      Medical College, Nanchong, China.
AD  - Clinical Medical School, Chengdu University of Traditional Chinese Medicine, 
      Chengdu, China.
FAU - Zhang, Quan-Bo
AU  - Zhang QB
AD  - Department of Gerontology, Affiliated Hospital of North Sichuan Medical College, 
      Nanchong, China.
FAU - Mi, Qing-Sheng
AU  - Mi QS
AD  - Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United 
      States.
FAU - Zhou, Jing-Guo
AU  - Zhou JG
AD  - Department of Rheumatology and Immunology, The First Affiliated Hospital of 
      Chengdu Medical College, Chengdu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190529
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Body Fluids/chemistry
MH  - Cytokines/biosynthesis
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Edema/chemically induced/prevention & control
MH  - Female
MH  - Foot
MH  - Gout/chemically induced/genetics/*prevention & control
MH  - Humans
MH  - Leukocytes, Mononuclear/drug effects/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Peritonitis/chemically induced/prevention & control
MH  - Phagocytosis/drug effects
MH  - Specific Pathogen-Free Organisms
MH  - Subcutaneous Tissue
MH  - T-Box Domain Proteins/biosynthesis/*deficiency/genetics/physiology
MH  - Uric Acid/toxicity
PMC - PMC6558421
OTO - NOTNLM
OT  - T-bet
OT  - cytokines
OT  - gout
OT  - inflammation
OT  - monosodium urate
EDAT- 2019/06/25 06:00
MHDA- 2020/07/21 06:00
PMCR- 2019/01/01
CRDT- 2019/06/25 06:00
PHST- 2019/02/14 00:00 [received]
PHST- 2019/05/13 00:00 [accepted]
PHST- 2019/06/25 06:00 [entrez]
PHST- 2019/06/25 06:00 [pubmed]
PHST- 2020/07/21 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01199 [doi]
PST - epublish
SO  - Front Immunol. 2019 May 29;10:1199. doi: 10.3389/fimmu.2019.01199. eCollection 
      2019.