PMID- 28550731
OWN - NLM
STAT- MEDLINE
DCOM- 20180501
LR  - 20180501
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 49
DP  - 2017 Aug
TI  - Xanthotoxin suppresses LPS-induced expression of iNOS, COX-2, TNF-alpha, and IL-6 via 
      AP-1, NF-kappaB, and JAK-STAT inactivation in RAW 264.7 macrophages.
PG  - 21-29
LID - S1567-5769(17)30194-7 [pii]
LID - 10.1016/j.intimp.2017.05.021 [doi]
AB  - Although xanthotoxin has been reported to possess skin-protective and 
      anti-oxidative properties, its anti-inflammatory capacity has not been studied to 
      date. Therefore, we investigated this role as well as the molecular mechanisms of 
      xanthotoxin in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. 
      Xanthotoxin inhibited production of nitric oxide (NO), prostaglandin E(2) 
      (PGE(2)), tumor necrosis factor (TNF-alpha), and interleukin-6 (IL-6) by the 
      LPS-induced macrophages in a concentration-dependent manner. It also suppressed 
      the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 
      (COX-2) expression at the protein levels and iNOS, COX-2, TNF-alpha, and IL-6 at the 
      mRNA levels. At a molecular level, the effects were related to 
      xanthotoxin-mediated attenuation of the LPS-induced transcriptional and 
      DNA-binding activity of activator protein-1 (AP-1). This attenuation was 
      associated with decreased phosphorylation of c-Fos, but not c-Jun. Xanthotoxin 
      also displayed a suppressive effect on the transcriptional and DNA-binding 
      activity of nuclear transcription factor kappa-B (NF-kappaB) by inhibiting p65 
      nuclear translocation. In addition, xanthotoxin significantly reduced the 
      phosphorylation at signal transducers and activators of transcription 1 (STAT1, 
      Ser 727 and Tyr 701) and STAT3 (Tyr 705), as well as Janus kinase (JAK) 1 and 2 
      in LPS-induced RAW 264.7 macrophages. Finally, xanthotoxin suppressed the 
      LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 
      and p38 mitogen-activated protein kinase (MAPK). Taken together, these results 
      indicate that xanthotoxin decreases NO, PGE(2), TNF-alpha, and IL-6 production by 
      downregulation of the NF-kappaB, AP-1, and JAK/STAT signaling pathways in LPS-induced 
      RAW 264.7 macrophages.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Lee, Seung-Bin
AU  - Lee SB
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical 
      Sciences, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of 
      Korea.
FAU - Lee, Woo Seok
AU  - Lee WS
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical 
      Sciences, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of 
      Korea.
FAU - Shin, Ji-Sun
AU  - Shin JS
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, Republic of Korea.
FAU - Jang, Dae Sik
AU  - Jang DS
AD  - Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung 
      Hee University, Seoul 130-701, Republic of Korea.
FAU - Lee, Kyung Tae
AU  - Lee KT
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee 
      University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical 
      Sciences, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of 
      Korea. Electronic address: ktlee@khu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20170524
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - U4VJ29L7BQ (Methoxsalen)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Inflammation/*drug therapy/immunology
MH  - Interleukin-6/genetics/metabolism
MH  - Janus Kinases/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology
MH  - Methoxsalen/*pharmacology
MH  - Mice
MH  - NF-kappa B/genetics/*metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/*metabolism
MH  - RAW 264.7 Cells
MH  - STAT Transcription Factors/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
OTO - NOTNLM
OT  - Activator protein-1
OT  - Janus kinase-signal transducers and activators of transcription
OT  - Nuclear factor-kappaB
OT  - Xanthotoxin
EDAT- 2017/05/28 06:00
MHDA- 2018/05/02 06:00
CRDT- 2017/05/28 06:00
PHST- 2017/03/08 00:00 [received]
PHST- 2017/05/16 00:00 [revised]
PHST- 2017/05/19 00:00 [accepted]
PHST- 2017/05/28 06:00 [pubmed]
PHST- 2018/05/02 06:00 [medline]
PHST- 2017/05/28 06:00 [entrez]
AID - S1567-5769(17)30194-7 [pii]
AID - 10.1016/j.intimp.2017.05.021 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2017 Aug;49:21-29. doi: 10.1016/j.intimp.2017.05.021. Epub 
      2017 May 24.