PMID- 24975507
OWN - NLM
STAT- MEDLINE
DCOM- 20150331
LR  - 20140801
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 28
IP  - 7
DP  - 2014 Oct
TI  - alpha-Lipoic acid (alpha-LA) inhibits the transcriptional activity of interferon 
      regulatory factor 1 (IRF-1) via SUMOylation.
PG  - 1242-8
LID - S0887-2333(14)00108-8 [pii]
LID - 10.1016/j.tiv.2014.06.003 [doi]
AB  - Osteoarthritis (OA), one of the most common joint disorders, is one of the 
      leading causes of disability among the elderly. Proinflammatory cytokines, such 
      as interleukin (IL)-1beta, which is synthesized locally by synovial cells and 
      chondrocytes, have been shown to play a critical role in sustaining cartilage 
      damage in arthritis by creating an imbalance between cartilage degradation and 
      the repair process. Alpha-lipoic acid (alpha-LA), which is synthesized in animal and 
      plant tissues, has demonstrated its protective effects in a variety of diseases. 
      However, whether or not LA has a protective effect in OA is still unknown. In 
      this study, we found that alpha-LA inhibits the IL-1beta-induced increase in matrix 
      metallopeptidase 3 (MMP-3) and matrix metallopeptidase 13 (MMP-13) expression and 
      activity. Our data also demonstrate that interferon regulatory factor 1 (IRF-1) 
      participates in the induction of MMP-3 and MMP-13. However, alpha-LA treatment did 
      not change IRF-1 levels. Importantly, we found that alpha-LA increases SUMOylation of 
      IRF-1, which attenuates IRF-1's transcriptional activity. Finally, we found that 
      alpha-LA treatment leads to an increase in SUMO-1, but not in SUMO-2 or SUMO-3. Taken 
      together, this study shows that alpha-LA exerts anti-inflammatory effects in an 
      IL-1beta-stimulated chondrocyte model, thereby suggesting a potential protective 
      effect of alpha-LA in OA.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Sun, Tao
AU  - Sun T
AD  - Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China.
FAU - Gao, Fuyu
AU  - Gao F
AD  - Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China.
FAU - Lin, Xiaoyan
AU  - Lin X
AD  - Department of Endocrine, Yantai Zhifu Hospital, Yantai 2960319, Shandong 
      Province, China.
FAU - Yu, Ruixiang
AU  - Yu R
AD  - Department of Endocrine, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China.
FAU - Zhao, Yong
AU  - Zhao Y
AD  - Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China.
FAU - Luan, Jingjie
AU  - Luan J
AD  - Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China.
FAU - Li, Hongyan
AU  - Li H
AD  - Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China.
FAU - Song, Mingzhu
AU  - Song M
AD  - Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, 
      China. Electronic address: songmz866@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20140626
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (IRF1 protein, human)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Interleukin-1beta)
RN  - 0 (SUMO-1 Protein)
RN  - 0 (SUMO1 protein, human)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chondrocytes/*drug effects/metabolism
MH  - Humans
MH  - Interferon Regulatory Factor-1/*metabolism
MH  - Interleukin-1beta/pharmacology
MH  - Matrix Metalloproteinase 13/genetics/metabolism
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Osteoarthritis/metabolism
MH  - SUMO-1 Protein/metabolism
MH  - Sumoylation
MH  - Thioctic Acid/*pharmacology
MH  - Transcription, Genetic
OTO - NOTNLM
OT  - Chondrocyte
OT  - Interferon regulatory factor 1
OT  - Interleukin (IL)-1beta
OT  - Lipoic acid
OT  - Osteoarthritis
OT  - SUMOylation
EDAT- 2014/07/01 06:00
MHDA- 2015/04/01 06:00
CRDT- 2014/07/01 06:00
PHST- 2014/02/01 00:00 [received]
PHST- 2014/05/07 00:00 [revised]
PHST- 2014/06/18 00:00 [accepted]
PHST- 2014/07/01 06:00 [entrez]
PHST- 2014/07/01 06:00 [pubmed]
PHST- 2015/04/01 06:00 [medline]
AID - S0887-2333(14)00108-8 [pii]
AID - 10.1016/j.tiv.2014.06.003 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2014 Oct;28(7):1242-8. doi: 10.1016/j.tiv.2014.06.003. Epub 
      2014 Jun 26.