PMID- 31570011
OWN - NLM
STAT- MEDLINE
DCOM- 20200408
LR  - 20200408
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 41
IP  - 6
DP  - 2019 Dec
TI  - Trace amine associated receptor 1 (TAAR1) expression and modulation of 
      inflammatory cytokine production in mouse bone marrow-derived macrophages: a 
      novel mechanism for inflammation in ulcerative colitis.
PG  - 577-585
LID - 10.1080/08923973.2019.1672178 [doi]
AB  - Context: Tissue resident macrophages and peripherally infiltrating macrophages 
      play a prominent role in maintaining homeostasis in the gastrointestinal tract 
      (GIT), though aberrant activation is implicated in inflammatory conditions, 
      including ulcerative colitis (UC). Recent metabolomic studies indicate that 
      tyramine (TYR) is elevated in the stool of patients with UC. TYR activates the 
      mammalian trace amine associated receptor 1 (TAAR1). Our previous work identified 
      TAAR1 expression in mixed populations of immune cells, whereas a limited number 
      of other studies have identified TAAR1-dependent effects in cytokine secretion 
      and gene expression in T-cells and B-cells.Objective: To investigate whether 
      TAAR1 may serve as a novel target for an anti-inflammatory therapeutic in UC, we 
      explored TAAR1 expression in mouse bone marrow-derived macrophages (BMDMs), and 
      its upregulation and activation in response to LPS and TYR.Results: Here, we 
      demonstrate for the first time that TAAR1 is expressed in BMDM and undergoes 
      agonist-induced upregulation. Additionally, TYR elicits significant increases in 
      inflammatory cytokine gene expression in non-polarized and LPS-polarized BMDM, 
      and the TAAR1 antagonist EPPTB inhibits the TYR-mediated upregulation of TAAR1 
      and inflammatory cytokine gene expression in BMDM. Conclusions: Our data suggest 
      that TAAR1 is a mediator of macrophage inflammation and a potential therapeutic 
      target to attenuate UC symptomology.
FAU - Bugda Gwilt, Katlynn
AU  - Bugda Gwilt K
AUID- ORCID: 0000-0001-9616-6934
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.
AD  - Center for Drug Discovery, Northeastern University, Boston, MA, USA.
FAU - Olliffe, Neva
AU  - Olliffe N
AD  - Department of Biology, Northeastern University, Boston, MA, USA.
AD  - Honors Program, Northeastern University, Boston, MA, USA.
FAU - Hoffing, Rachel A
AU  - Hoffing RA
AD  - Department of Biology, Northeastern University, Boston, MA, USA.
FAU - Miller, Gregory M
AU  - Miller GM
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.
AD  - Center for Drug Discovery, Northeastern University, Boston, MA, USA.
AD  - Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20191001
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - XMC8VP6RI2 (Trace amine-associated receptor 1)
SB  - IM
MH  - Animals
MH  - Bone Marrow
MH  - Colitis, Ulcerative/*metabolism/pathology
MH  - Cytokines/*biosynthesis
MH  - *Gene Expression Regulation
MH  - Inflammation/metabolism/pathology
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/*metabolism/pathology
MH  - Mice
MH  - Receptors, G-Protein-Coupled/*biosynthesis
OTO - NOTNLM
OT  - Tyramine
OT  - bone marrow-derived macrophages
OT  - colitis
OT  - cytokines
OT  - trace amine associated receptor
EDAT- 2019/10/02 06:00
MHDA- 2020/04/09 06:00
CRDT- 2019/10/02 06:00
PHST- 2019/10/02 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/10/02 06:00 [entrez]
AID - 10.1080/08923973.2019.1672178 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2019 Dec;41(6):577-585. doi: 
      10.1080/08923973.2019.1672178. Epub 2019 Oct 1.