PMID- 30590577
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200217
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 31
IP  - 4
DP  - 2019 Mar 28
TI  - A partial agonist for retinoid X receptor mitigates experimental colitis.
PG  - 251-262
LID - 10.1093/intimm/dxy089 [doi]
AB  - Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's 
      disease, is an intractable disease of the gastrointestinal tract. Multiple 
      environmental factors, including food ingredients, have been implicated in the 
      development of these diseases. For example, animal fat-rich diets are 
      predisposing factors for ulcerative colitis, whereas n-3 unsaturated fatty acids 
      such as docosahexaenoic acid (DHA) show protective effects in experimental 
      colitis and are negatively correlated with the incidence of ulcerative colitis 
      and Crohn's disease. Given that DHA exhibits agonistic activity on retinoid X 
      receptor (RXR), activation of RXR could be a therapeutic strategy for IBD. 
      However, conventional full RXR agonists are known to show considerable adverse 
      effects. We therefore took advantage of a partial RXR agonist, CBt-PMN, to 
      minimize the adverse effects, and evaluated its efficacy in dextran sodium 
      sulfate-induced colitis. Administration of CBt-PMN efficiently ameliorated the 
      symptoms of colitis. This effect was attributed to the down-regulation of 
      pro-inflammatory cytokines such as Tnf and Il6 in colon-infiltrating monocytes. 
      Down-regulation of pro-inflammatory cytokines by CBt-PMN was also evident in 
      lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDMs). Among many 
      RXR-associated nuclear receptors, activation of peroxisome proliferator-activated 
      receptor delta (PPARdelta) and nuclear hormone receptor 77 (Nur77) suppressed cytokine 
      production by BMDMs. These observations suggest that the activation of PPARdelta/RXR 
      and Nur77/RXR heterodimers by CBt-PMN through the permissive mechanism is 
      responsible for diminishing the monocyte-mediated inflammatory response in the 
      gut. Our data highlight the importance of RXR activation in the regulation of 
      colitis.
CI  - (c) The Japanese Society for Immunology. 2018. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Onuki, Masayoshi
AU  - Onuki M
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Watanabe, Masaki
AU  - Watanabe M
AD  - Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
FAU - Ishihara, Narumi
AU  - Ishihara N
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Suzuki, Koichiro
AU  - Suzuki K
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
AD  - Japan Society for the Promotion of Science, Kominachi Business Center Building, 
      Chiyoda-ku, Tokyo, Japan.
FAU - Takizawa, Kei
AU  - Takizawa K
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Hirota, Masato
AU  - Hirota M
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Yamada, Takahiro
AU  - Yamada T
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Egawa, Aiko
AU  - Egawa A
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Shibahara, Osamu
AU  - Shibahara O
AD  - Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
FAU - Nishii, Midori
AU  - Nishii M
AD  - Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
FAU - Fujihara, Michiko
AU  - Fujihara M
AD  - Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
FAU - Makishima, Makoto
AU  - Makishima M
AD  - Division of Biochemistry, Department of Biomedical Sciences, Nihon University 
      School of Medicine, Tokyo, Japan.
FAU - Takahashi, Daisuke
AU  - Takahashi D
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Furusawa, Yukihiro
AU  - Furusawa Y
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
FAU - Kakuta, Hiroki
AU  - Kakuta H
AD  - Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
FAU - Hase, Koji
AU  - Hase K
AD  - Division of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 
      Japan.
AD  - International Research and Development Center for Mucosal Vaccines, The Institute 
      of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 
      (1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic 
      acid)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nr4a1 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (PPAR delta)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Triazoles)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Colitis/*metabolism
MH  - Cytokines/metabolism
MH  - Dextran Sulfate
MH  - Disease Models, Animal
MH  - Docosahexaenoic Acids/metabolism
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Inflammatory Bowel Diseases/*metabolism
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism
MH  - PPAR delta/metabolism
MH  - Protein Binding
MH  - Retinoid X Receptors/agonists/*metabolism
MH  - Tetrahydronaphthalenes/pharmacology/*therapeutic use
MH  - Triazoles/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - Nur77
OT  - PPARdelta
OT  - RXR
OT  - inflammatory bowel disease
OT  - monocytes
EDAT- 2018/12/28 06:00
MHDA- 2020/02/18 06:00
CRDT- 2018/12/28 06:00
PHST- 2018/07/28 00:00 [received]
PHST- 2018/12/24 00:00 [accepted]
PHST- 2018/12/28 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2018/12/28 06:00 [entrez]
AID - 5261218 [pii]
AID - 10.1093/intimm/dxy089 [doi]
PST - ppublish
SO  - Int Immunol. 2019 Mar 28;31(4):251-262. doi: 10.1093/intimm/dxy089.