PRENATAL EXPOSURE TO DEXAMETHASONE ALTERS THE
CYTOKINE PROFILE: IMPLICATIONS FOR PEPTIC DISEASE
Leão P, Oliveira M, Botelho C M, Mariz J, Lamas N, Sousa N
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal;
Prenatal dexamethasone (DEX) exposure triggers several changes in nervous, autonomic and immune systems later in adulthood. As a result, we have shown that prenatal administration of DEX is associated with an increase vulnerability to peptic disease in adult life. In this study, we aim to clarify the impact of DEX-induced deregulation in the secretion of pro- (IL-1and IL-6) and anti-inflamatory (IL-10) cytokines, as well as COX-1 and COX-2 in the gastric mucosa.
Introduction
Methods
Results
Rat dams were exposed to the synthetic glucocorticoid dexamethasone (1mg/Kg) on days 18 and 19 of gestation.
COX-1, COX-2 and cytokine (IL-1β, IL-6 and IL-10)
expression was assessed, by quantitative RT-PCR, in different regions of the stomach mucosa (fundus, body and antrum) of adult rats exposed to DEX (n=5) and CONT (n=5) in the prenatal period.
IL-1β profile in Gastric Mucosa
Relative expression of mRNA obtained by RT-PCR
in the gastric mucosa of prenatal DEX-treated
animals. IL-1 pro-inflamatory cytokine show a
high significantly expression level in body region. P<0,05.
Conclusion
These observations, which identify glucocorticoid-sensitive gastric regions (antrum and body) in female progeny, pave way for future studies designed to understand how early life events can predispose individuals for developing peptic disease in adult life, and may contribute for the study of future therapeutic approaches to this pathology.
Neurosciences
Research Domain
University of Minho
–
Portugal
www.ecsaude.uminho.pt/icvs/
Antrum
CONT DEX
0.0 2.5 5.0 7.5
Re
al
tiv
e
ex
pr
es
si
on
o
f m
RN
A
Body
CONT DEX
0.0 0.5 1.0 1.5 2.0 2.5 3.0
3.5 *
Re
al
tiv
e
ex
pr
es
si
on
o
f m
RN
A
Fundus
CONT DEX
0 1 2
Re
al
tiv
e
ex
pr
es
si
on
o
f m
RN
A
IL-1 Profile
Pro-inflamatory IL-6 Cytokine
Interleukin IL-6 mRNA changes significantly (p<0,05) in DEX animals in antrum region. Interleukin-6 (IL-6) is proinflammatory cytokine that produces multifunctional effects. It is involved in the regulation of immune reactions, but it has also been shown to be associated with tumor progression including inhibition of cancer cells apoptosis.
Antrum
CONT DEX
0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08
*
R
el
at
iv
e
ex
pr
es
si
on
o
f
m
R
N
A
Body
CONT DEX
0.000 0.025 0.050 0.075 0.100
R
el
at
iv
e
ex
pr
es
si
on
o
f
m
R
N
A
Fundus
CONT DEX
0.00 0.01 0.02
R
el
at
iv
e
ex
pr
es
si
on
o
f
m
R
N
A
IL-6 Profile
Antrum
CONT DEX
0 1 2
R
el
at
iv
e
ex
pr
es
si
on
o
f mR
N
A
Body
CONT DEX
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
4.5 *
R
el
at
iv
e
ex
pr
es
si
on
o
f m
R
N
A
CONT DEX
0 1 2
Fundus
R
el
at
iv
e
ex
pr
es
si
on
o
f m
R
N
A
IL-10 Profile
Antrum
CONT DEX
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
R
el
at
iv
e
ex
pr
es
si
on
o
f mR
N
A
Body
CONT DEX
0.0 0.5 1.0 1.5
*
Re
la
ti
ve
e
xp
re
ss
io
n
of
mRN
A
Fundus
CONT DEX
0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45
R
el
at
iv
e
ex
pr
es
si
on
o
f mR
N
A
COX - 1 Profile
Antrum
CONT DEX
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
R
el
at
iv
e
ex
pr
es
si
on
o
f
m
R
N
A
Body
CONT DEX
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
0.9 **
R
el
at
iv
e
ex
pr
es
si
on
o
f
m
R
N
A
Fundus
CONT DEX
0 1 2 3
R
el
at
iv
e
ex
pr
es
si
on
o
f
m
R
N
A
COX-2 Profile
COX-2 (non-constitutive) isoform expression in Gastric Mucosa
Effect of DEX-treated animals on mRNA expression of COX-2 .
Total RNA was extracted from gastric mucosa.
The results reveals that body gastric region is significantly
sensitive (p<0,01) to COX-2 expression in DEX-treated animals.
This may be implicated with pathophysiological reactions such inflammation.
COX-1 (constitutive) isoform expression in Gastric Mucosa
COX-1 is constitutively expressed in the gastrointestinal tract in
large quantities and has been suggested to maintain mucosal
integrity through continous generation of prostaglandins. Our
observations reveals a significantly alterations on COX -1 expression in DEX-treated rats (p<0,05) especially in body of gastric mucosa.
Anti-inflamatory IL-10 Cytokine
Anti-inflamatory cytokines play an important role in downregulation of inflammation and the prevention of neoplasic disorders. IL-10 are implicated in regulatory suppression of gastric inflammation.
In this study we observed a high significantly IL-10 expression in body of the stomach (p<0,05).
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