PMID- 34288557
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20220531
IS  - 2050-4527 (Electronic)
IS  - 2050-4527 (Linking)
VI  - 9
IP  - 4
DP  - 2021 Dec
TI  - ORMDL3 overexpression facilitates FcepsilonRI-mediated transcription of proinflammatory 
      cytokines and thapsigargin-mediated PERK phosphorylation in RBL-2H3 cells.
PG  - 1394-1405
LID - 10.1002/iid3.489 [doi]
AB  - INTRODUCTION: The chromosomal region 17q21 harbors the human orosomucoid-like 3 
      (ORMDL3) gene and has been linked to asthma and other inflammatory diseases. 
      ORMDL3 is involved in the unfolded protein response (UPR), lipid metabolism, and 
      inflammatory reactions. We investigated the effects of ORMDL3 overexpression in 
      RBL-2H3 cells to determine the contribution of ORMDL3 to inflammatory disease 
      development. METHODS: We generated ORMDL3 stably overexpressing RBL-2H3 cells to 
      assess degranulation, transcriptional upregulation of interleukin-4 (IL-4), tumor 
      necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and 
      mitogen-activated protein kinase (MAPK) phosphorylation via FcepsilonRI. In addition, 
      we examined the effects of ORMDL3 overexpression on thapsigargin (TG)-mediated 
      proinflammatory cytokine transcription and UPR by monitoring MAPK, protein 
      kinase-like endoplasmic reticulum kinase (PERK), and inositol-requiring enzyme 1 
      (IRE1) phosphorylation. RESULTS: Overexpression of ORMDL3 enhanced IL-4, TNF-alpha, 
      and MCP-1 expression after FcepsilonRI cross-linking, whereas the 
      sphingosine-1-phosphate (S1P) agonist FTY720 suppressed this enhancement. There 
      was no significant difference in degranulation and MAPK phosphorylation via 
      FcepsilonRI-mediated activation between vector-transfected and ORMDL3-overexpressing 
      cells. ORMDL3 overexpression accelerated TG-mediated PERK phosphorylation, while 
      MAPK phosphorylation and proinflammatory cytokine expression showed no 
      significant changes in ORMDL3-overexpressing cells. CONCLUSIONS: Our findings 
      suggest that ORMDL3 plays an important role in regulating proinflammatory 
      cytokine expression via the S1P pathway and selectively affects the UPR pathway 
      in mast cells.
CI  - (c) 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & 
      Sons Ltd.
FAU - Ogi, Kazuhiro
AU  - Ogi K
AUID- ORCID: 0000-0002-7358-7784
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Takabayashi, Tetsuji
AU  - Takabayashi T
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Tomita, Kaori
AU  - Tomita K
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Sakashita, Masafumi
AU  - Sakashita M
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Morikawa, Taiyo
AU  - Morikawa T
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Ninomiya, Takahiro
AU  - Ninomiya T
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Okamoto, Masayuki
AU  - Okamoto M
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Narita, Norihiko
AU  - Narita N
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
FAU - Fujieda, Shigeharu
AU  - Fujieda S
AD  - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and 
      Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210719
PL  - England
TA  - Immun Inflamm Dis
JT  - Immunity, inflammation and disease
JID - 101635460
RN  - 0 (Cytokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (ORMDL3 protein, human)
RN  - 0 (Orosomucoid)
RN  - 0 (Receptors, IgE)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Cell Degranulation
MH  - *Cytokines/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Humans
MH  - Membrane Proteins/genetics/metabolism
MH  - Orosomucoid
MH  - Phosphorylation
MH  - *Receptors, IgE/genetics
MH  - Thapsigargin/pharmacology
PMC - PMC8589398
OTO - NOTNLM
OT  - FTY720
OT  - ORMDL3
OT  - S1P
OT  - UPR
OT  - mast cell
COIS- The authors declare that there are no conflict of interests.
EDAT- 2021/07/22 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/07/19
CRDT- 2021/07/21 13:53
PHST- 2021/07/01 00:00 [revised]
PHST- 2021/02/12 00:00 [received]
PHST- 2021/07/05 00:00 [accepted]
PHST- 2021/07/22 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/21 13:53 [entrez]
PHST- 2021/07/19 00:00 [pmc-release]
AID - IID3489 [pii]
AID - 10.1002/iid3.489 [doi]
PST - ppublish
SO  - Immun Inflamm Dis. 2021 Dec;9(4):1394-1405. doi: 10.1002/iid3.489. Epub 2021 Jul 
      19.