PMID- 34831128
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 10
IP  - 11
DP  - 2021 Oct 27
TI  - Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells.
LID - 10.3390/cells10112906 [doi]
LID - 2906
AB  - Mast cells (MCs) act as primary effectors in inflammatory and allergic reactions 
      by releasing intracellularly-stored inflammatory mediators in diseases. The two 
      major pathways for MC activation are known to be immunoglobulin E (IgE)-dependent 
      and -independent. Although IgE-dependent signaling is the main pathway to MC 
      activation, IgE-independent pathways have also been found to serve pivotal roles 
      in the pathophysiology of various inflammatory conditions. Recent studies have 
      shown that human and mouse MCs express several regulatory receptors such as 
      toll-like receptors (TLRs), CD48, C300a, and GPCRs, including mas-related GPCR-X2 
      (MRGPRX2). MRGPRX2 has been reported as a novel GPCR that is expressed in MCs 
      activated by basic secretagogues, neurokinin peptides, host defense antimicrobial 
      peptides, and small molecule compounds (e.g., neuromuscular blocking agents) and 
      leads to MC degranulation and eicosanoids release under in vitro experimental 
      condition. Functional analyses of MRGPRX2 and Mrgprb2 (mouse ortholog) indicate 
      that MRGPRX2 is involved in MC hypersensitivity reactions causing 
      neuroinflammation such as postoperative pain, type 2 inflammation, 
      non-histaminergic itch, and drug-induced anaphylactic-like reactions. In this 
      review, we discuss the roles in innate immunity through functional studies on 
      MRGPRX2-mediated IgE-independent MC activation and also the therapeutic potential 
      of MRGPRX2 inhibitors on allergic and inflammatory diseases.
FAU - Ogasawara, Hiroyuki
AU  - Ogasawara H
AUID- ORCID: 0000-0003-2193-4868
AD  - Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan.
FAU - Noguchi, Masato
AU  - Noguchi M
AUID- ORCID: 0000-0002-3092-0946
AD  - Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research 
      Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan.
AD  - Office of Research Development and Sponsored Projects, Shinanomachi Campus, Keio 
      University, Tokyo 160-8582, Japan.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20211027
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Receptors, G-Protein-Coupled)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mast Cells/*metabolism
MH  - Models, Biological
MH  - Neurogenic Inflammation/pathology
MH  - Receptors, G-Protein-Coupled/*antagonists & inhibitors
MH  - Signal Transduction
PMC - PMC8616451
OTO - NOTNLM
OT  - MRGPRX2
OT  - MRGPRX2 inhibitor
OT  - host defense
OT  - mast cell activation
OT  - neurogenic inflammation
OT  - non-histaminergic itch
OT  - pseudoallergic reaction
OT  - type 2 inflammation
COIS- The authors declare no competing interests.
EDAT- 2021/11/28 06:00
MHDA- 2022/01/14 06:00
PMCR- 2021/10/27
CRDT- 2021/11/27 01:14
PHST- 2021/09/29 00:00 [received]
PHST- 2021/10/21 00:00 [revised]
PHST- 2021/10/25 00:00 [accepted]
PHST- 2021/11/27 01:14 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/10/27 00:00 [pmc-release]
AID - cells10112906 [pii]
AID - cells-10-02906 [pii]
AID - 10.3390/cells10112906 [doi]
PST - epublish
SO  - Cells. 2021 Oct 27;10(11):2906. doi: 10.3390/cells10112906.