PMID- 36675245
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230202
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 2
DP  - 2023 Jan 15
TI  - DHA Induces Cell Death through the Production of ROS and the Upregulation of CHOP 
      in Fibroblast-like Synovial Cells from Human Rheumatoid Arthritis Patients.
LID - 10.3390/ijms24021734 [doi]
LID - 1734
AB  - Rheumatoid arthritis (RA) is an inflammatory disease marked by a massive 
      proliferation of synovial cells in the joints. In this study, we investigated the 
      pro-apoptotic effects of docosahexaenoic acid (DHA) in human fibroblast-like 
      synovial cells from RA patients (RA-FLS). An in vitro study using MH7A cells 
      showed that DHA treatment induced caspase-8-dependent apoptosis in a 
      dose-dependent manner and reduced the TNF-alpha-mediated induction of MMP-9 and 
      IL-1beta. DHA also induced the phosphorylation of eIF2alpha, the expression of the ER 
      stress markers ATF4 and C/EBP homologous protein (CHOP), and death receptor 5 
      (DR5). The knockdown of CHOP or DR5 increased cell viability and reduced 
      apoptosis in DHA-treated cells. Furthermore, the knockdown of CHOP reduced 
      DHA-mediated DR5 expression, while the overexpression of CHOP increased DR5 
      expression. We also found that DHA treatment induced the accumulation of reactive 
      oxygen species (ROS), and pretreatment with the anti-oxidant Tiron effectively 
      abrogated not only the expression of CHOP and DR5, but also DHA-induced 
      apoptosis. Under this condition, cell viability was increased, while PARP-1 
      cleavage and caspase-8 activation were reduced. All the findings were reproduced 
      in human primary synovial cells obtained from RA patients. These results suggest 
      that the DHA-mediated induction of ROS and CHOP induced apoptosis through the 
      upregulation of DR5 in RA-FLSs, and that CHOP could be used as a therapy for RA.
FAU - Jeong, Mini
AU  - Jeong M
AUID- ORCID: 0000-0003-3279-4215
AD  - Division of Allergy and Clinical Immunology, Department of Internal Medicine, 
      Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, 
      Republic of Korea.
FAU - Shin, Jong-Il
AU  - Shin JI
AD  - Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, 
      Gwangin-gu, Seoul 05029, Republic of Korea.
FAU - Cho, Jaewook
AU  - Cho J
AD  - Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, 
      Gwangin-gu, Seoul 05029, Republic of Korea.
FAU - Jeon, Yong-Joon
AU  - Jeon YJ
AD  - Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, 
      Gwangin-gu, Seoul 05029, Republic of Korea.
FAU - Kim, Jin-Hyun
AU  - Kim JH
AD  - Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, 
      Gwangin-gu, Seoul 05029, Republic of Korea.
FAU - Youn, Jeehee
AU  - Youn J
AD  - Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, 
      Seoul 04763, Republic of Korea.
FAU - Lee, Kyungho
AU  - Lee K
AUID- ORCID: 0000-0002-5220-1387
AD  - Department of Biological Sciences, Konkuk University, 120 Neungdong-ro, 
      Gwangin-gu, Seoul 05029, Republic of Korea.
AD  - Korea Hemp Institute, Konkuk University, 120 Neungdong-ro, Gwangin-gu, Seoul 
      05029, Republic of Korea.
LA  - eng
GR  - 2017M3A9G7072745/National Research Foundation of Korea/
GR  - 2017R1D1A1B03031743/National Research Foundation of Korea/
GR  - 2022R1F1A1074572/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20230115
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Reactive Oxygen Species)
RN  - EC 3.4.22.- (Caspase 8)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 147336-12-7 (Transcription Factor CHOP)
SB  - IM
MH  - Humans
MH  - Up-Regulation
MH  - Cell Line, Tumor
MH  - Reactive Oxygen Species/metabolism
MH  - Caspase 8/metabolism
MH  - *Docosahexaenoic Acids/pharmacology
MH  - Apoptosis
MH  - *Arthritis, Rheumatoid
MH  - Fibroblasts/metabolism
MH  - Transcription Factor CHOP/genetics/metabolism
PMC - PMC9865349
OTO - NOTNLM
OT  - CHOP
OT  - DHA
OT  - ER stress
OT  - RA-FLSs
OT  - ROS
OT  - apoptosis
COIS- All authors declare that they have no competing interests.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/01/15
CRDT- 2023/01/21 01:29
PHST- 2022/11/06 00:00 [received]
PHST- 2022/12/29 00:00 [revised]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/01/21 01:29 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/15 00:00 [pmc-release]
AID - ijms24021734 [pii]
AID - ijms-24-01734 [pii]
AID - 10.3390/ijms24021734 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 15;24(2):1734. doi: 10.3390/ijms24021734.