Objectives: Unfolded proteins in the endoplasmic reticulum (ER) cause an ER stress response and can result in various pathologic conditions, including inflammation. Otitis media is the most common disease in otolaryngology and is associated with inflammation. The pathophysiology of chronic otitis media is not well understood; we therefore investigated the expression pattern of ER stress-related mRNAs in chronic otitis media. Methods: Specimens were obtained from 47 patients with chronic otitis media over a period of 2 years. Expression levels of 6 ER stress transcription factors were quantitatively assessed using real-time RT-PCR. Results: The mRNA expression of sXBP1 was significantly higher in the otorrhea present group than in the otorrhea absent group (p < 0.05). ATF6 expression was significantly higher in the ossicle destruction group than in the ossicle intact group (p < 0.05). mRNA expression of the 6 ER stress-related genes did not differ significantly between those patients with positive microbial cultures versus those with negative cultures (p > 0.05) or those with facial nerve dehiscence versus those without facial nerve dehiscence (p > 0.05). Conclusions: sXBP1 appears to be involved in chronic otitis media-associated inflammation, including otorrhea. ATF6 is associated with the destruction of ossicles. Our results suggest that certain ER stress-related genes are expressed in chronic otitis media-associated inflammation.

1.
Rovers
MM
,
Schilder
AG
,
Zielhuis
GA
,
Rosenfeld
RM
.
Otitis media
.
Lancet
.
2004
Feb
;
363
(
9407
):
465
73
.
[PubMed]
0140-6736
2.
Proctor
B
.
The Development of the Middle Ear Spaces and their Surgical Significance
.
J Laryngol Otol
.
1964
Jul
;
78
(
07
):
631
48
.
[PubMed]
0022-2151
3.
Celli
J
,
Tsolis
RM
.
Bacteria, the endoplasmic reticulum and the unfolded protein response: friends or foes?
Nat Rev Microbiol
.
2015
Feb
;
13
(
2
):
71
82
.
[PubMed]
1740-1526
4.
Yoshida
H
.
ER stress and diseases
.
FEBS J
.
2007
Feb
;
274
(
3
):
630
58
.
[PubMed]
1742-464X
5.
Sovolyova
N
,
Healy
S
,
Samali
A
,
Logue
SE
.
Stressed to death - mechanisms of ER stress-induced cell death
.
Biol Chem
.
2014
Jan
;
395
(
1
):
1
13
.
[PubMed]
1431-6730
6.
Sano
R
,
Reed
JC
.
ER stress-induced cell death mechanisms
.
Biochim Biophys Acta
.
2013
Dec
;
1833
(
12
):
3460
70
.
[PubMed]
0006-3002
7.
Cybulsky
AV
,
Takano
T
,
Papillon
J
,
Bijian
K
.
Role of the endoplasmic reticulum unfolded protein response in glomerular epithelial cell injury
.
J Biol Chem
.
2005
Jul
;
280
(
26
):
24396
403
.
[PubMed]
0021-9258
8.
Hetz
C
.
The unfolded protein response: controlling cell fate decisions under ER stress and beyond
.
Nat Rev Mol Cell Biol
.
2012
Jan
;
13
(
2
):
89
102
.
[PubMed]
1471-0072
9.
Ron
D
,
Walter
P
.
Signal integration in the endoplasmic reticulum unfolded protein response
.
Nat Rev Mol Cell Biol
.
2007
Jul
;
8
(
7
):
519
29
.
[PubMed]
1471-0072
10.
Bertolotti
A
,
Zhang
Y
,
Hendershot
LM
,
Harding
HP
,
Ron
D
.
Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response
.
Nat Cell Biol
.
2000
Jun
;
2
(
6
):
326
32
.
[PubMed]
1465-7392
11.
Schröder
M
,
Kaufman
RJ
.
ER stress and the unfolded protein response
.
Mutat Res
.
2005
Jan
;
569
(
1-2
):
29
63
.
[PubMed]
0027-5107
12.
Montane
J
,
Cadavez
L
,
Novials
A
.
Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes
.
Diabetes Metab Syndr Obes
.
2014
Feb
;
7
:
25
34
.
[PubMed]
1178-7007
13.
Kaser
A
,
Lee
AH
,
Franke
A
,
Glickman
JN
,
Zeissig
S
,
Tilg
H
, et al
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease
.
Cell
.
2008
Sep
;
134
(
5
):
743
56
.
[PubMed]
0092-8674
14.
Keestra-Gounder
AM
,
Byndloss
MX
,
Seyffert
N
,
Young
BM
,
Chávez-Arroyo
A
,
Tsai
AY
, et al
NOD1 and NOD2 signalling links ER stress with inflammation
.
Nature
.
2016
Apr
;
532
(
7599
):
394
7
.
[PubMed]
0028-0836
15.
Bauer
C
,
Jenkins
H
.
Diagnostic Audiology. Cummings Otolaryngology: Head & Neck Surgery
. 6th ed.
Philadelphia (PA)
:
Elsevier Saunders
;
2015
.
16.
Chen
Y
,
Brandizzi
F
.
IRE1: ER stress sensor and cell fate executor
.
Trends Cell Biol
.
2013
Nov
;
23
(
11
):
547
55
.
[PubMed]
0962-8924
17.
Sou
SN
,
Ilieva
KM
,
Polizzi
KM
.
Binding of human BiP to the ER stress transducers IRE1 and PERK requires ATP
.
Biochem Biophys Res Commun
.
2012
Apr
;
420
(
2
):
473
8
.
[PubMed]
0006-291X
18.
Wang
T
,
Yuan
Y
,
Zou
H
,
Yang
J
,
Zhao
S
,
Ma
Y
, et al
The ER stress regulator Bip mediates cadmium-induced autophagy and neuronal senescence
.
Sci Rep
.
2016
Dec
;
6
(
1
):
38091
.
[PubMed]
2045-2322
19.
Lee
WS
,
Sung
MS
,
Lee
EG
,
Yoo
HG
,
Cheon
YH
,
Chae
HJ
, et al
A pathogenic role for ER stress-induced autophagy and ER chaperone GRP78/BiP in T lymphocyte systemic lupus erythematosus
.
J Leukoc Biol
.
2015
Feb
;
97
(
2
):
425
33
.
[PubMed]
0741-5400
20.
Chen
L
,
Xu
S
,
Liu
L
,
Wen
X
,
Xu
Y
,
Chen
J
, et al
Cab45S inhibits the ER stress-induced IRE1-JNK pathway and apoptosis via GRP78/BiP
.
Cell Death Dis
.
2014
May
;
5
(
5
):
e1219
.
[PubMed]
2041-4889
21.
Lee
JS
,
Kim
MG
,
Hong
SM
,
Na
SY
,
Byun
JY
,
Park
MS
, et al
Changing patterns of bacterial strains in adults and children with otitis media in korean tertiary care centers
.
Clin Exp Otorhinolaryngol
.
2014
Jun
;
7
(
2
):
79
86
.
[PubMed]
1976-8710
22.
Guo
FJ
,
Xiong
Z
,
Lu
X
,
Ye
M
,
Han
X
,
Jiang
R
.
ATF6 upregulates XBP1S and inhibits ER stress-mediated apoptosis in osteoarthritis cartilage
.
Cell Signal
.
2014
Feb
;
26
(
2
):
332
42
.
[PubMed]
0898-6568
23.
Yamada
H
,
Nakajima
T
,
Domon
H
,
Honda
T
,
Yamazaki
K
.
Endoplasmic reticulum stress response and bone loss in experimental periodontitis in mice
.
J Periodontal Res
.
2015
Aug
;
50
(
4
):
500
8
.
[PubMed]
0022-3484
24.
Scott
DL
,
Wolfe
F
,
Huizinga
TW
.
Rheumatoid arthritis
.
Lancet
.
2010
Sep
;
376
(
9746
):
1094
108
.
[PubMed]
0140-6736
25.
Rao
J
,
Yue
S
,
Fu
Y
,
Zhu
J
,
Wang
X
,
Busuttil
RW
, et al
ATF6 mediates a pro-inflammatory synergy between ER stress and TLR activation in the pathogenesis of liver ischemia-reperfusion injury
.
Am J Transplant
.
2014
Jul
;
14
(
7
):
1552
61
.
[PubMed]
1600-6135
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