2022 Impact Factor: 1.5
2023 CiteScore: 2.6
pISSN: 1735-1502
eISSN: 1735-5249
Chairman:
Mostafa Moin, M.D.
Editors-in-Chief:
Masoud Movahedi, M.D.
Vol 10, No 3 (2011)
Articles
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Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard lung patients. Mustard lung is the general description for the chronic obstructive pulmonary disease induced by sulfur mustard(SM). Pulmonary disease was diagnosed as the most important disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent developed during Wars. Iraqi forces frequently used it against Iranian during Iran –Iraq in the 1980–1988. Peribronchial fibrosis result from airway remodeling that include excess of collagen of extracellular matrix deposition in the airway wall. Some of Smads families in association with TGF-β are involved in airway remodeling due to lung fibrosis. In the present study we compared the mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall biopsies of chemical-injured patients with non-injured patients as control.
We used airway wall biopsies of ten unexposed patients and fifteen SM-induced patients. Smads expression was evaluated by RT-PCR followed by bands densitometry.
Expression levels of Smad3 and Smad4 in SM exposed patients were upregulated but Smad2 and Smad7 was not significantly altered.
Our results revealed that Smad3, and 4 may be involved in airway remodeling process in SM induced patients by activation of TGF-β. Smad pathway is the most represented signaling mechanism for airway remodeling and peribronchial fibrosis. The complex of Smads in the nucleus affects a series of genes that results in peribronchial fibrosis in SM- induced patients. -
Multiple Sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disorder of the central nervous system (CNS), which mainly affects young adults. Activated T lymphocytes promote the neuro-inflammatory cascade of MS by secreting pro-inflammatory cytokines and play a significant role in its pathogenesis. T lymphocytes may trigger the inflammation, which in turn leads to axonal loss and neurodegeneration observed in the course of MS.
Currently, there is no cure for MS, however, one of the most promising neuroprotective research tools consists of the use of bone marrow derived mesenchymal stem cells (MSC). This method promotes immune system regulation and possibly induces neurological repair and re-myelination of the damaged axons. Recent studies have shown that MSC exert an immune regulatory function and induce T regulatory-cell proliferation, therefore, it may serve as a potentially useful treatment for immune-mediated diseases such as MS.
In this pilot study a group of MS patients underwent MSC therapy and we assayed the expression of an X-linked transcription factor, FoxP3, as a specific marker of T Regulatory cells in peripheral blood, prior to and after the treatment. Using q RT-PCR for measurement of expression of FoxP3 by peripheral blood mononuclear cells, we found that in all subjects, except for one, the expression of FoxP3 at 6 months after intrathecal injection of MSC was significantly higher than the levels prior to treatment.
Such significant enhanced expression of FoxP3 associated with clinical stability. Findings from this pilot study further support the potential of bone marrow derived MSC for treatment of MS patients. -
Dendritic cells (DCs) play an important role in induction of cellular immune responses. It seems that DCs that reside in different organs may be distinct in their ability to induce immune responses. This study was done to address the differences between spleen and liver DCs in induction of immune response and/or tolerance.
CD11c+ DCs were separated from the liver and spleen of C57BL/6 mice and pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. 6×105 MOG35-55 pulsed spleen or liver DCs were injected in foot pad of different groups of mice. Control groups received unpulsed DCs. After 5 days, the mononuclear cells (MNCs) of the regional lymph nodes were isolated from immunized mice for cytokine assays and lymphocyte transformation test. To study the immunologic or tolerogenic effects of DCs, three weeks after immunization of mice with MOG pulsed liver or spleen DCs, experimental autoimmune encephalomyelitis (EAE) was induced in DC-immunized mice by injection of MOG along with complete Freund’s adjuvant. Our results showed that spleen DCs were more potent in stimulating lymph node T cells as illustrated in lymphocyte transformation test. Moreover IL-10 production was higher in mice immunized with liver DCs compared with those immunized with splenic DCs (p=0.017). However, no significant difference in IFN-γ production was observed between two groups. We also found that liver DCs+MOG immunized mice displayed a significantly delayed disease onset compared with spleen DCs+MOG immunized mice and the control groups. The disease score was also milder in liver DCs immunized mice compared with other groups.
It seems that the higher IL-10 production induced by the liver DCs may be one of the main factors in down regulation of immune responses in this organ. It can be concluded also that the liver DCs may inhibit the progress of EAE by shifting the cytokines profile. -
Allergic asthma is a complex and chronic inflammatory airway disease. Interleukin-17 is a pro-inflammatory cytokine which plays critical role in the pathogenesis of allergic asthma. It has been reported that β-arrestin2 regulated the development of allergic asthma at a proximal step in the inflammatory cascade. In this study, the influence of β-arrestin2 on Interleukin-17 production and expression of CD4+ T lymphocytes in a murine asthma model was investigated.
Splenic CD4+ T lymphocytes from wild-type mice and those from a murine asthma model were purified. CD4+ T lymphocytes from a murine asthma model were transfected with siRNAs targeting the β-arrestin2 or were pretreated with the ERK1/2 inhibitor,PD98059. After stimulation, the protein expression of β-arrestin2、phosphorylated- ERK1/2 and IL-17 were detection by Western blot; the mRNA expression of IL-17 were detected by real-time PCR; the accumulation of IL-17 in supernatants were detected by ELISA.
We found that β-arrestin2、phosphorylated-ERK1/2 and IL-17 expression in CD4+ T lymphocytes from a murine asthma model was increased compared with those from wild- type mice(p<0.01). Treatment of CD4+ T lymphocytes with siRNAs targeting the β-arrestin2 down-regulated phosphorylated- ERK 1/2 and IL-17 expression (p < 0.01). PD98059 decreased IL-17 production and expression in CD4+ T lymphocytes in a murine asthma model (p < 0.05).
We conclude that β-arrestin2 stimulated IL-17 production and expression of CD4+ T lymphocytes in a murine asthma model. The effect was partly mediated by ERK 1/2 activation. Targeting β-arrestin2 biological activity could be a valid therapeutic approach for the treatment of allergic asthma. -
Allergic rhinitis (AR) is a very frequent disease which is not only characterized by nasal symptoms, but also with behavioural changes. This study evaluated the serum serotonin levels in patients with pollen-induced AR during and outside the pollen season.
One-hundred-two (56 females, 46 males, median age: 28.7 years) were included in this study: 56 with seasonal AR (SAR) evaluated outside the pollen season and so without allergic inflammation and symptoms, and 46 with SAR evaluated during the pollen season with symptoms. Blood specimens were collected to assess serum concentrations of serotonin and to compare results to scores of a Quality of Life (QoL) questionnaire which was performed in all subjects.
Serotonin serum concentrations were higher in AR patients out of pollen season than in (p<0.01). There was a very strong direct relationship between QoL and serotonin concentrations.
This preliminary study demonstrates that SAR influences serotonin concentrations and that serum serotonin could serve as a biomarker in AR patients with behavioural symptoms. -
Study of KIR Expression and HLA Ligands in CD56+ Lymphocytes of Drug Resistant Tuberculosis Patients
Analysis of receptor–ligand interactions in the context of diseases necessitates to understand how HLA–KIR genotypes function in diseases. Although CD56+ lymphocytes are derived from multiple lineages, they share a functional association with immunosurviellance and antimicrobial responses.
The present study aimed to determine whether KIR phenotype in CD56 lymphocytes and corresponding HLA-class 1 ligands are associated with multidrug resistance tuberculosis (MDR-TB). We compared the frequencies of HLA-C and HLA-BW4 genes, the expression of KIRs 2DL1/2DS1, 2DL2/2DL3, 3DL1, and 2DS4 and the combinations of HLA/KIR in 32 Nifamycin and Isoniazid-resistant TB with those in 68 drug non resistant (NR) sputum smear positive pulmonary TB patients. PCR-SSP and flow cytometry were performed for HLA and KIRs typing, respectively.
We showed no significant differences between inhibitory or activating KIRs as well as HLA ligands in MDR TB patients compared with NR-TB . The combinations of inhibitory KIR-HLA ligands in MDR-TB were much more prevalent, but not statistically significant than in NR patients (p=0.07). The frequency of MDR patients with all HLA-C and HLA- BW4 ligands was higher than NR-TB (p<0.009). Conversely, the percentage of MDR patients having only one kind of HLA gene was significantly lower than NR-TB (p<0.01). We conclude that the expression of inhibitory KIRs with corresponding HLA ligands genes, and/or co-existence of three HLA class 1 ligands for inhibitory KIRs may be associated with drug resistance in pulmonary tuberculosis. -
Contact dermatitis is frequent skin pathology and eyelids are one of the more frequent locations of this pathology. The objective of the present work was to study the population distribution of periocular dermatitis, determine the allergens which most frequently indicate positive in patch tests and in provocative use tests, and analyse the clinical relevance of the positive tests.
Patients with periocular dermatitis (N=93) underwent a thorough physical examination and a patch test with standard series. According to clinical suspicions, 76 patients underwent a patch test with specific series. Finally a provocative use test was done for 36 patients with suspected products that the patients brought. The tests were classified according their relevance.
The most frequently observed allergen in the patch tests (with standard and specific series) was nickel followed by mercury, and anti-glaucoma drops in the provocative use tests with patients products.
Patients’ sex, age, occupation, clinical status, presence of associated periocular symptoms, and presence of atopic or seborrheic dermatitis and/or rosacea did not relate with relevance.
We conclude that a clinical diagnosis may not always be made with patch tests with standard and specific series due to lack of relevance. It is important to do provocative use tests with the products suspected as allergens in those cases where patch tests with standard and specific series indicated positive for more than one allergen. -
Phosphodiesterases (PDE) hydrolyse intracellular cAMP and cGMP to inactive 5’ monophosphates. Decreased level of cAMP is involved in the pathogenesis of asthma. We and others have shown that phosphodiesterases were upregulated in the lung of allergic rats, and Bacilli Calmette-Guérin (BCG) induced the production of cAMP in vitro. However, it is unclear how BCG’s effect asthma and whether it is related to PDEs.
In this study, BCG was intraperitoneally injected into male Sprague-Dawley rats sensitized and later the rats were challenged with ovabumin/pertusis. The inflammation in lungs was measured. Airway hyperresponsiveness was determined using MedLab software after intravenous methacholine challenge. Furthermore, cAMP level and adenylate cyclase activity in lungs were analyzed by ELISA, phosphodiesterases activities were analyzed by HPLC, while PDEs mRNA levels in lungs was analyzed by reverse transcription-polymerase chain reaction. Administration of BCG significantly attenuated allergen-induced lung inflammatory response and hyper responsiveness as compared with vehicle treatment. Furthermore, the levels of cAMP in lungs were significantly increased in BCG-treated allergic rats. Interestingly, administration of BCG decreased the activity of cAMP-PDE, but not adenylyl cyclase (AC), activity in lungs of animals. Furthermore, pretreatment with BCG significantly decreased the mRNA levels of PDE4A, 4C, 5 and 8, which were induced in lungs of allergic rats.
BCG administration attenuated airway inflammatory response and bronchial hyper responsiveness in rats, which are the most important symptoms in asthma. The decreased PDEs mRNA and inhibited cAMP-PDE activities by BCG contribute, at least in part, prevention of allergen-induced airway inflammation and asthma in rats. -
Inhalation of fungal spores is shown to participate in the development of allergic rhinitis symptoms. In this study, relation between presence of Alternaria in the human nasal cavity and allergic rhinitis is assessed.
In a case-control study, 58 allergic rhinitis patients were compared with a well-matched control group of fifty healthy volunteers for sensitization to Alternaria (by skin prick test) and detection of Alternaria in their nasal mucous by conventional methods (microscopy with Methylene Blue stain and culture in Sabourad dextrose agar). Severity of the disease was determined according to the ARIA classification. Pearson chi-square test was applied to compare the proportional difference between the study groups for detection of Alternaria in the nasal cavity, and sensitization to Alternaria.
Relation between detection of Alternaria and allergic rhinitis was significant [OR = 18.18 (4.02-82.50)] In addition, sensitization to Alternaria showed a significant relation with the disease [OR = 2.8 (2.1-3.8)]. There was a significant relation between the presence of Alternaria in the nasal cavity and sensitization to Alternaria [OR = 10.4 (3.8-28.3)]. Both sensitization to Alternaria and presence of Alternaria in the nasal cavity did not have a significant relation with the severity of allergic rhinitis. This study suggests Alternaria as a major allergen that its presence in the nasal cavity and subsequent development of sensitization have significant role in the induction of allergic rhinitis. -
Severe congenital neutropenia (SCN) is a rare primary immunodeficiency. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR. Also, recently G6PC3 as a rare gene in SCN has been reported.
Patients with G6PC3 often have cardiac and/or urogenital malformations. Two patients with persistent severe neutropenia, recurrent infections and maturation arrest at promyelocyte-myelocyte stage in their bone marrow were assessed in this study.
Both patients showed structural heart disease and one of them also showed urogenital anomaly. Sequence analyses of G6PC3 in 2 patients revealed two different homozygous mutations, one in exon 6 (Asn 313 fs), and the other in exon 3 (Ser 139 Met), the latter is a new mutation which has not been reported in previous studies.
It can be concluded that G6PC3 is one of the responsible gene for SCN in Iranian patients. Based on the results, a new mutation in G6PC3 observed in one patient.
