Original Article
Zahra Faghih; Saeideh Sadat Shobeiri; Ali Ariafar; Mohsen Sarkarian; Shahryar Zeighami; Nazanin Nazari; Saeed Abbasi-Sarvak; Nasrollah Erfani
Volume 13, Issue 4 , December 2016, Pages 237-248
Abstract
Background: Cytotoxic CD8+ T cells, as essential parts of the adaptive immune
system, play pivotal roles in anti-tumor immune responses. It is well documented that
cytokine expression profiles and activation status of these cells during anti-tumor
immune responses affect the outcome of host-tumor ...
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Background: Cytotoxic CD8+ T cells, as essential parts of the adaptive immune
system, play pivotal roles in anti-tumor immune responses. It is well documented that
cytokine expression profiles and activation status of these cells during anti-tumor
immune responses affect the outcome of host-tumor interaction. Objective: To
investigate the percentages of CD8+ lymphocytes and their subsets in tumor draining
lymph nodes of patients with bladder cancer. Methods: Forty-five patients with bladder
cancer, candidate for radical cystectomy, were recruited. Mononuclear cells were
isolated from draining lymph nodes using Ficoll-Hypaque gradient centrifugation, and
were activated by PMA/Ionomycin in the presence of Golgi inhibitors. The cells were
then permeabilized and stained with appropriate flourochrome conjugated antibodies
against CD3, CD8, IFN-γ, IL-17 and IL-4 molecules. Data were collected on a fourcolor
flow cytometer and analyzed by CellQuestPro software. Results: Despite no
difference in the frequency of IL-17 producing CD8+ (Tc17) lymphocytes, the mean
expression of IL-17 in this subset was significantly elevated in high-grade patients
(p=0.011). The percentage of double positive IFN-γ/IL-17 CD8+ lymphocytes was also
significantly increased in node positive patients compared to node negative ones
(p=0.046). Our results also demonstrated that the percentage of IFN-γ producing CD8+
(Tc1) lymphocytes was significantly increased in the patients with higher histological
grade compared to those with lower ones (p=0.038). Conclusion: IFN-γ and IL-17
producing CD8+ T cells may increase in advanced stages of bladder cancer, but their
correlation with tumor prognosis remains to be investigated.
Original Article
Mohammadreza Yazdani; Shahdad Khosropanah; Ahmad Hosseini; Mehrnoosh Doroudchi
Volume 13, Issue 4 , December 2016, Pages 249-262
Abstract
Background: Atherosclerosis is a chronic inflammatory disease affecting large and
medium arteries. CD4+ T cells are known to play a role in the progression of the
disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role
in the disease and their reduction in acute coronary ...
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Background: Atherosclerosis is a chronic inflammatory disease affecting large and
medium arteries. CD4+ T cells are known to play a role in the progression of the
disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role
in the disease and their reduction in acute coronary syndrome is recently shown.
Objective: To investigate the frequency of nTreg subsets in the peripheral blood of
patients with atherosclerosis. Methods: Confirmation of atherosclerosis was done by
angiography and 15 ml heparinized blood was obtained from each of the 13 nondiabetic
patients and 13 non-diabetic, non-smoker individuals with normal/insignificant
coronary artery disease which was also confirmed by angiography. Lipid profiles of the
patients and controls were measured at the time of sampling. Mononuclear cells were
used for both RNA extraction and immunophenotyping by real-time PCR and
flowcytometry techniques, respectively. Results: In natural Treg subsets, the frequency
of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than
patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated
nTregs) was significantly higher in controls compared with patients (p=0.02). However,
the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory) increased in
patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3
were higher in control group than in patients (p=0.015 and p=0.017, respectively).
Moreover, the TGF-β gene expression showed a decrease in the peripheral blood
mononuclear cells of patients compared with controls (p=0.03). Conclusion: Decrease
in both subsets of resting and activated nTregs along with a decrease in the expression
of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes
in these subsets, which may as well be correlated with a more inflammatory profile in
their lymphocytes.
Original Article
Reza Feyzi; Mohammad Hossein Boskabady; Seyedeh Masoumeh Seyed hosseini Tamijani; Houshang Rafatpanah; Seyed Abdolrahim Rezaei
Volume 13, Issue 4 , December 2016, Pages 263-273
Abstract
Background: Several biological and medical benefits of Saffron, Crocus sativus
(Iridaceae), have been demonstrated. However, mechanisms of actions for purified
constituents are greatly unknown. Objective: To examine the effects of Safranal, a main
constituent of Saffron stigma, on cell viability and ...
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Background: Several biological and medical benefits of Saffron, Crocus sativus
(Iridaceae), have been demonstrated. However, mechanisms of actions for purified
constituents are greatly unknown. Objective: To examine the effects of Safranal, a main
constituent of Saffron stigma, on cell viability and cytokine profile of peripheral blood
mononuclear cells (PBMC) were examined. Methods: Effects of Safranal at 0.1, 0.5
and 1 mM concentrations were evaluated on cell viability and production of interleukin
4 (IL-4), IL-10 and interferon-γ (IFN-γ) from non-stimulated and phytohemagglutinin
(PHA) stimulated PBMCs, compared to 0.1 mM dexamethasone and saline. Results: In
stimulated cells, different concentrations of Safranal caused significant decrease of
lymphocytes viability (p<0.001 for all concentrations). All concentrations of Safranal
inhibited IFN-γ and IL-10 secretion in stimulated cells (p<0.01). In addition, high
concentration of Safranal significantly decreased cell viability of non-stimulated
PBMCs (p<0.001). The effect of 1 mM Safranal on IL-4 secretion was less than
dexamethasone (p<0.05). Safranal showed a stimulatory effect on IFN-γ secretion in
non-stimulated cells. The IFN-γ/IL-4 ratio at the presence of two higher Safranal
concentrations both in non-stimulated and stimulated cells were significantly higher
than those of control and PHA stimulated groups, respectively (p<0.05). Conclusion:
The IFN-γ/IL-4 ratio increases in the presence of Safranal which indicates an effect on
Th1/Th2 balance. Therefore, Safranal may have therapeutic effects in inflammatory
diseases associated with Th1/Th2 imbalance.
Original Article
Ali Moravej; Mohammad-Hossein Karimi; Bita Geramizadeh; Mahdokht Hossein Aghdaie; Omid Kohi-Hoseinabadi; Salimeh Ebrahimnezhad
Volume 13, Issue 4 , December 2016, Pages 274-288
Abstract
Background: Mesenchymal stem cells (MSCs) are considered as effective therapeutic
cells in transplantation due to their immunomodulatory activities. However, precise
mechanism of MSCs immunomodulatory activity is not completely understood.
Objectives: To study the role of Immunoglobulin-like transcripts-3 ...
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Background: Mesenchymal stem cells (MSCs) are considered as effective therapeutic
cells in transplantation due to their immunomodulatory activities. However, precise
mechanism of MSCs immunomodulatory activity is not completely understood.
Objectives: To study the role of Immunoglobulin-like transcripts-3 (ILT3)
immunomodulatory receptor in immune tolerance induced by MSCs in skin
transplantation model and induction of tolerogenic dendritic cells (Tol-DCs) by MSCs
through up-regulation of ILT3. Methods: C57BL/6 skin grafts were transplanted to the
back of BALB/c mice. Recipient mice received MSCs on days 0, 1 and 2 post
transplantation. On days 2, 5 and 10 post skin transplantation, ILT3 and forkhead box
P3 (FOXP3) expression in the spleens of MSCs treated mice were evaluated.
Furthermore, MSCs and DCs were co-cultured in cell culture plates and transwell
systems. Then, the expressions of ILT3 mRNA and protein in MSC-treated DCs were
evaluated. Additionally, MSC-treated DCs were co-cultured with allogeneic T-cells and
FOXP3 expression in T-cells was evaluated. Results: The expression of ILT3 and
FOXP3 were higher in the splenocytes of MSCs-treated mice early post-transplantation.
Furthermore, we observed that MSC-treated DCs can increase FOXP3 expression in Tcells.
But, we could not find any differences in ILT3 expression between MSC-treated
DCs and untreated ones. Conclusion: One of the mechanisms underlying MSCs
immunomodulatory function could be up-regulating ILT3 expression in splenocytes.
But our results did not support the hypothesis that MSCs induce Tolergenic DCs by upregulation
of ILT3.
Original Article
Zahra Meshkat; Amir Teimourpour; Samira Rashidian; Mohsen Arzanlou; Roghayeh Teimourpour
Volume 13, Issue 4 , December 2016, Pages 289-295
Abstract
Background: Tuberculosis is a life threatening disease that is partially prevented by
BCG vaccine. Development of more effective vaccines is an urgent priority in TB
control. Ag85a and Tb10.4 are the members of culture filter protein (CFP) of M.
tuberculosis that have high immunogenicity. Objective: ...
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Background: Tuberculosis is a life threatening disease that is partially prevented by
BCG vaccine. Development of more effective vaccines is an urgent priority in TB
control. Ag85a and Tb10.4 are the members of culture filter protein (CFP) of M.
tuberculosis that have high immunogenicity. Objective: To analyze the
immunogenicity of Ag85a-Tb10.4 DNA vaccine by enzyme-linked immunosorbent
assay (ELISA). Methods: In this study a previously described plasmid DNA vaccine
encoding Ag85a-Tb10.4 was used to examine its capability in the stimulation of
immune responses in an animal model. Female BALB/c mice were vaccinated with 100
μg of purified recombinant vector intramuscularly 3 times at two-week intervals and the
levels of five cytokines including IFN-γ, IL-12, IL-4, IL-10 and TGF-β were measured.
Results: The levels of IFN-γ and IL-12 for the mice following immunization with
Ag85A-Tb10.4 was significantly greater than that of the BCG and control group
(p<0.05). However there was no significant difference in the levels of IL-4, IL-10 and
TGF-β between groups. Conclusion: IFN-γ and IL-12 Th1 cytokines increased
significantly in mice vaccinated with Ag85a-TB10.4 DNA vaccine in comparison to the
control and BCG groups. Our results may serve as groundwork for further research into
the prevention and treatment of tuberculosis.
Original Article
Behrouz Gharesi-Fard; Fatemeh Mobasher-Nejad; Fatemeh Nasri
Volume 13, Issue 4 , December 2016, Pages 296-308
Abstract
Background: Pre-eclampsia (PE) is known as a main factor contributing to
fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth
week of gestation. The balance of T helper subsets is essential to sustain a normal
pregnancy and preventing fetomaternal complications. Objective: ...
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Background: Pre-eclampsia (PE) is known as a main factor contributing to
fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth
week of gestation. The balance of T helper subsets is essential to sustain a normal
pregnancy and preventing fetomaternal complications. Objective: To investigate
differences in the levels of transcription factors and cytokine gene expression of
Th1/Th2/Th17/Treg subsets within decidual and chorionic layers of placentas from 15
PE-afflicted and 15 healthy Iranian women in their third trimester of pregnancy.
Methods: Using Quantitative real-time PCR (Q-PCR), The expression of T-BET,
GATA-3, ROR-ɣt, FOXP3, and cytokines, including IL-1, IL-6, TNF-α, IFN-γ, IL-4,
IL-31, IL-17, IL-23, TGF-β1, TGF-β2, TGF-β3, and IL-35 in the placenta were
compared at mRNA levels between groups. Results: FOXP3 and GATA-3 were
significantly down-regulated, while T-BET was up-regulated in PE deciduae compared
to the control group (p<0.0001, p<0.02, and p<0.01, respectively). Concerning the
chorionic samples, FOXP3 significantly decreased, while ROR-γt increased in the PE
placentas compared to the healthy ones (p<0.0006 and p<0.02, respectively). Besides,
most inflammatory cytokines were up-regulated, while anti-inflammatory cytokines
were down-regulated in the PE placentas. Additionally, TNF-α/IL-35, IFN-ɣ/IL-35, IL-
6/IL-35, and IL-23/IL-35 ratios were significantly higher (p<0.01) and IL-35/IL-17 ratio
was significantly lower (p<0.05) in the pre-eclamptic patients compared to the healthy
controls. Conclusion: Our results shed more light on the contribution of
Th1/Th2/Th17/Treg balance within placenta in the fate of a normal pregnancy.
Moreover, regulatory T cells and IL-35 seem to play a central role in the regulation of
all subsets.
Original Article
Zeinab Tavakkol Afshari; Hamid Reza Rahimi; Seyed Morteza Ehteshamfar; Rashin Ganjali; Fatemeh Tara; Abbas Shapouri Moghadam
Volume 13, Issue 4 , December 2016, Pages 309-316
Abstract
Background: Pre-eclampsia is the most common critical condition during pregnancy.
Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta
(IL-1β) increase in pregnant women with pre-eclampsia, compared to normal pregnant
women. Objective: To investigate the polymorphisms ...
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Background: Pre-eclampsia is the most common critical condition during pregnancy.
Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta
(IL-1β) increase in pregnant women with pre-eclampsia, compared to normal pregnant
women. Objective: To investigate the polymorphisms of IL-1β (C+3954T), TNF-α (G-
308A), and (G-238A) in preeclemptic women northeastern Iran. Methods: This study
was conducted on 153 preeclamptic women (case group) and 150 healthy pregnant
women (control group), admitted to Ghaem and Imam Reza hospitals of Mashhad, Iran.
IL-1β (C+3954T), TNF- α (G-238A) and TNF-α (G-308A) gene polymorphisms in the
promoter region were screened by polymerase chain reaction. Data were analyzed,
using SPSS version 16.0. Results: The mean age of the participants in the case and
control groups was 28.2 ± 6.1 and 27.1 ± 6.3 years, respectively (P=0.68). The
frequency of G-308A polymorphism was significantly higher in the case group,
compared to the control group (p<0.001). However, no significant relationship was
found between IL-1β genotype and pre-eclampsia (p=0.39). The frequency of TNF- α
(G-238A) AA genotype was significantly higher in the case group, while GG genotype
was less frequently detected in the case group, compared to the control group (p<0.001
for both genotypes). Moreover, the frequencies of AA genotypes of -238 TNF-α and G-
308A polymorphisms were significantly higher in the case group, compared to the
control group (p<0.001). Conclusion: The significant correlation between inflammation
promoting genotypes of TNF-α and Pre-eclampsia is noteworthy and provides evidence
on the contribution of immune related genes in this disease.
Short Paper
Mohammad Reza Sobhan; Mahmood Farshchian; Ali Hoseinzadeh; Hamid Reza Ghasemibasir; Ghasem Solgi
Volume 13, Issue 4 , December 2016, Pages 317-323
Abstract
Background: As a chronic inflammatory condition, psoriasis results from an interaction
between genetic and immunologic factors in a predisposing environment. In spite of
compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)-
10 and IL-22 have not been sufficiently ...
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Background: As a chronic inflammatory condition, psoriasis results from an interaction
between genetic and immunologic factors in a predisposing environment. In spite of
compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)-
10 and IL-22 have not been sufficiently investigated. Objective: To assess the serum
levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls.
Methods: A total of 28 patients with psoriasis were compared with 28 age and sexmatched
healthy subjects. Psoriasis Area and Severity Index (PASI) criteria were used
to measure the severity of the disease. Serum levels of IL-10 and IL-22 were measured
in both groups and compared. Results: The mean serum level of IL-10 was 89.5±18.7 in
patients compared to 117.2±23.4 pg/ml in the controls (p=0.36). Also, serum level of
IL-22 was 284.1±49.7 in patients versus 425.4±82.8 pg/ml in control group (p=0.17).
There was a significant direct correlation between levels of IL-10 and IL-22 in patients
group (p=0.0005). The clinical severity of psoriasis was significantly correlated with
high levels of IL-22 (p<0.0001).Conclusions: The decreased levels of IL-10 in psoriatic
patients and direct correlation between higher levels of IL-22 and disease severity
support the clinical implication of both cytokines in psoriasis.
