PMID- 29751576
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20240318
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 5
DP  - 2018 May 3
TI  - Thymoquinone Suppresses IRF-3-Mediated Expression of Type I Interferons via 
      Suppression of TBK1.
LID - 10.3390/ijms19051355 [doi]
LID - 1355
AB  - Interferon regulatory factor (IRF)-3 is known to have a critical role in viral 
      and bacterial innate immune responses by regulating the production of type I 
      interferon (IFN). Thymoquinone (TQ) is a compound derived from black cumin 
      (Nigella sativa L.) and is known to regulate immune responses by affecting 
      transcription factors associated with inflammation, including nuclear 
      factor-κB (NF-κB) and activator protein-1 (AP-1). However, the role 
      of TQ in the IRF-3 signaling pathway has not been elucidated. In this study, we 
      explored the molecular mechanism of TQ-dependent regulation of enzymes in IRF-3 
      signaling pathways using the lipopolysaccharide (LPS)-stimulated murine 
      macrophage-like RAW264.7 cell line. TQ decreased mRNA expression of the 
      interferon genes IFN-α and IFN-β in these cells. This inhibition was 
      due to its suppression of the transcriptional activation of IRF-3, as shown by 
      inhibition of IRF-3 PRD (III-I) luciferase activity as well as the 
      phosphorylation pattern of IRF-3 in the immunoblotting experiment. Moreover, TQ 
      targeted the autophosphorylation of TANK-binding kinase 1 (TBK1), an upstream key 
      enzyme responsible for IRF-3 activation. Taken together, these findings suggest 
      that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would 
      subsequently decrease the production of type I IFN. TQ also regulated IRF-3, one 
      of the inflammatory transcription factors, providing a novel insight into its 
      anti-inflammatory activities.
FAU - Aziz, Nur
AU  - Aziz N
AUID- ORCID: 0000-0001-7696-1025
AD  - Department of Integrative Biotechnology and Biomedical Institute for Convergence 
      (BICS), Sungkyunkwan University, Suwon 16419, Korea. nuraziz@skku.edu.
FAU - Son, Young-Jin
AU  - Son YJ
AUID- ORCID: 0000-0001-8141-9927
AD  - Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea. 
      sony@sunchon.ac.kr.
FAU - Cho, Jae Youl
AU  - Cho JY
AD  - Department of Integrative Biotechnology and Biomedical Institute for Convergence 
      (BICS), Sungkyunkwan University, Suwon 16419, Korea. jaecho@skku.edu.
LA  - eng
PT  - Journal Article
DEP - 20180503
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Benzoquinones)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interferon Type I)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - O60IE26NUF (thymoquinone)
SB  - IM
MH  - Animals
MH  - Benzoquinones/*pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Interferon Regulatory Factor-3/*metabolism
MH  - Interferon Type I/*metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - RAW 264.7 Cells
MH  - RNA, Messenger/metabolism
PMC - PMC5983753
OTO - NOTNLM
OT  - IRF-3
OT  - TBK1
OT  - inflammation
OT  - thymoquinone
OT  - type I interferons
COIS- The authors declare no conflict of interest.
EDAT- 2018/05/13 06:00
MHDA- 2018/09/25 06:00
PMCR- 2018/05/01
CRDT- 2018/05/13 06:00
PHST- 2018/04/14 00:00 [received]
PHST- 2018/04/30 00:00 [revised]
PHST- 2018/05/02 00:00 [accepted]
PHST- 2018/05/13 06:00 [entrez]
PHST- 2018/05/13 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2018/05/01 00:00 [pmc-release]
AID - ijms19051355 [pii]
AID - ijms-19-01355 [pii]
AID - 10.3390/ijms19051355 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 May 3;19(5):1355. doi: 10.3390/ijms19051355.