9 research outputs found
Immune responses in defined subgroups of patients with pulmonary sarcoidosis
This thesis focuses on inflammatory responses in the airways of
sarcoidosis patients. Sarcoidosis is a T helper 1-mediated inflammatory
disease with unknown aetiology. HLA-DRB1*0301pos sarcoidosis patients
often present with an acute form of disease, i.e. Löfgren s syndrome,
usually with a very good prognosis. These patients also have expansions
of CD4+ T cells expressing the T cell receptor AV2S3 gene segment in
their lungs. The overall aim of these studies was to investigate the
inflammatory and immune regulatory responses in sarcoidosis and in
specific subgroups of patients, compared to healthy controls.
The cytokine profile in bronchoalveolar lavage fluid (BALF) of patients
revealed that the levels of mRNA and protein expression of
pro-inflammatory and Th1 associated cytokines were in general increased
in sarcoidosis patients compared to healthy individuals. In particular,
HLA-DRB1*0301neg patients expressed significantly increased levels of
pro-inflammatory and Th1 associated cytokines in their lungs as compared
to HLA-DRB1*0301pos patients and controls. A tendency to a higher
expression of TGF- beta1 was seen in DRB1*0301pos patients.
The study of BALF CD4+ T cells in patients revealed decreased mRNA levels
of the T regulatory cell-specific transcription factor, FOXP3, and of
regulatory associated genes IL-10 and CCR2. Furthermore, at the protein
level reduced frequencies of FOXP3- expressing BALF and blood CD4+ T
cells were observed in patients. The mean fluorescence intensity of FOXP3
expression in BALF FOXP3+ CD4+ cells of patients was also reduced. AV2S3+
CD4+ T cells expressed significantly reduced levels of FOXP3 and CCR2
compared to the other BALF CD4+ T cells. We did not find any differences
in the expression of CCR2, FOXP3, IL-10 and TGF-beta1 between patient
subgroups. Sarcoidosis patients expressed decreased levels of T-cell
immunoglobulin and mucin domain (TIM)-3 mRNA in their BALF CD4+ T cells,
as compared to healthy subjects, while IL-2 expression was increased in
patients. TIM molecules have been suggested to be important regulators of
immune functions. In addition, our data revealed an increased mRNA level
of IFN-gamma in non-Löfgren s patients as compared to Löfgren s patients,
while the mRNA level of TIM-1 was decreased.
Analyzing alveolar macrophages, we detected a significantly lower
expression of TLR2 in patients, in particular patients with Löfgren s
syndrome. We also observed that the gene expression of
fibrosis-associated CCL18 was higher in patients compared to controls.
There was a tendency to higher IL-23 levels in cultured BALF cells of
patients, but upon LPS-stimulation it was markedly more upregulated in
healthy controls.
In conclusion, the reduced immune regulatory response in the lungs of
sarcoidosis patients may result in an uncontrolled inflammation
particularly in non-Löfgren s patients, contributing to the pathogenesis
of this disease. AV2S3+ T cells in the lungs of Löfgren s patients seem
to have an effector function and may contribute to the eradication of a
postulated sarcoidosis antigen
Investigation on estrogen receptor alpha gene polymorphisms in Iranian women with recurrent pregnancy loss
Background: Recurrent pregnancy loss (RPL) is a multifactorial disorder. Environmental factors and genetics can affect pregnancy outcomes.\ud
Objective: Conflicting data suggest an association between estrogen receptor alpha (ESR1) gene polymorphisms and RPL. In this study, such association was investigated in Iranian women with RPL.\ud
Materials and Methods: In this case control study, blood samples were collected from 244 women with a history of three or more consecutive pregnancy losses and 104 healthy women with at least two live births. Using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control subjects.\ud
Results: The genotypic frequencies of -397C/T and -351A/G polymorphisms on ESR1were not significantly different between RPL and control groups (p=0.20 and p=0.09, respectively). A significantly negative correlation was observed between -397C/T and -351A/G (r=-0.852, p<0.001) in RPL women and complete linkage disequilibrium between the investigated polymorphisms was found (D’: 0.959; r-square= 0.758, p<0.001).\ud
Conclusion: This investigation suggests that the analyzed polymorphisms on ESR1gene are not associated with an increased risk of RPL in the studied populatio
Investigation on estrogen receptor alpha gene polymorphisms in Iranian women with recurrent pregnancy loss
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Investigating the Antiangiogenic, Anti-drug Resistance and Apoptotic Effects of Soy Isoflavone Extract Alone or in Combination with Docetaxel on Murine 4T1 Breast Tumor Model
Additional file 1: of Differential expression profiles of the salivary proteins SP15 and SP44 from Phlebotomus papatasi
Sequences of primers used in qRT-PCR. (XLS 24 kb