PMID- 27185659
OWN - NLM
STAT- MEDLINE
DCOM- 20171221
LR  - 20180411
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 110
DP  - 2016 Aug
TI  - Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via 
      induction of IL-10-producing regulatory T cells by modulating the function of 
      dendritic cells.
PG  - 111-121
LID - S1043-6618(16)30088-3 [pii]
LID - 10.1016/j.phrs.2016.04.030 [doi]
AB  - Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and 
      possesses various biological activities. Herein, we investigated the antiallergic 
      effects of imperatorin in asthmatic mice and explored the immunomodulatory 
      actions of imperatorin on immune cells. We used a murine model of ovalbumin 
      (OVA)-induced asthma to evaluate the therapeutic potential of imperatorin. 
      Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to 
      clarify whether imperatorin exerts an antiallergic effect through altering the 
      ability of DCs to regulate T cells. Oral administration of imperatorin to 
      OVA-sensitized and -challenged mice decreased serum OVA-specific immunoglobulin E 
      (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated 
      airway inflammation in a dose-dependent manner. Notably, secretions of Th2 
      cytokines and chemokines were reduced, and numbers of interleukin 
      (IL)-10-producing regulatory T cells (Tregs) increased in imperatorin-treated 
      mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but 
      enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared 
      to fully mature DCs, imperatorin-treated DCs expressed high levels of the 
      inducible costimulatory ligand (ICOSL) and Jagged1 molecules, and had the 
      regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells 
      in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell 
      proliferation and cytokine production. Imperatorin may possess therapeutic 
      potential against Th2-mediated allergic asthma not only via stimulating DC 
      induction of Tregs but also via direct inhibition of Th2 cell activation. These 
      findings provide new insights into how imperatorin affects the Th2 immune 
      response and the development of imperatorin as a Treg-type immunomodulatory agent 
      to treat allergic asthma.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Lin, Chu-Lun
AU  - Lin CL
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Hsiao, George
AU  - Hsiao G
AD  - Department of Pharmacology, College of Medicine, Taipei Medical University, 
      Taipei, Taiwan.
FAU - Wang, Ching-Chiung
AU  - Wang CC
AD  - School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 
      Taiwan.
FAU - Lee, Yueh-Lun
AU  - Lee YL
AD  - Department of Microbiology and Immunology, College of Medicine, Taipei Medical 
      University, Taipei, Taiwan. Electronic address: yllee@tmu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160513
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Anti-Allergic Agents)
RN  - 0 (Furocoumarins)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Icosl protein, mouse)
RN  - 0 (Inducible T-Cell Co-Stimulator Ligand)
RN  - 0 (Jag1 protein, mouse)
RN  - 0 (Jagged-1 Protein)
RN  - 130068-27-8 (Interleukin-10)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
RN  - K713N25C78 (imperatorin)
SB  - IM
MH  - Animals
MH  - Anti-Allergic Agents/*pharmacology
MH  - Asthma/immunology/metabolism/physiopathology/*prevention & control
MH  - Bronchial Hyperreactivity/immunology/metabolism/physiopathology/*prevention & 
      control
MH  - Bronchoconstriction/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/immunology/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Furocoumarins/*pharmacology
MH  - Immunoglobulin E/blood
MH  - Inducible T-Cell Co-Stimulator Ligand/immunology/metabolism
MH  - Interleukin-10/immunology/*metabolism
MH  - Jagged-1 Protein/immunology/metabolism
MH  - Lung/*drug effects/immunology/metabolism/physiopathology
MH  - Lymphocyte Activation/drug effects
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Ovalbumin
MH  - Phenotype
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes, Regulatory/*drug effects/immunology/metabolism
MH  - Th2 Cells/*drug effects/immunology/metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Allergic asthma
OT  - Bone marrow-derived dendritic cells
OT  - Imperatorin
OT  - Interleukin-10
OT  - Regulatory T cells
EDAT- 2016/05/18 06:00
MHDA- 2017/12/22 06:00
CRDT- 2016/05/18 06:00
PHST- 2016/02/01 00:00 [received]
PHST- 2016/04/22 00:00 [revised]
PHST- 2016/04/29 00:00 [accepted]
PHST- 2016/05/18 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/12/22 06:00 [medline]
AID - S1043-6618(16)30088-3 [pii]
AID - 10.1016/j.phrs.2016.04.030 [doi]
PST - ppublish
SO  - Pharmacol Res. 2016 Aug;110:111-121. doi: 10.1016/j.phrs.2016.04.030. Epub 2016 
      May 13.