Iranian Journal of Allergy, Asthma and Immunology
Year:2014 | Volume:13 | Issue:6|Papers Count:11

Rho-kinase is an effector molecule of RhoA, a monomeric GTP-binding protein, and causes Ca2+ sensitization through inactivation of myosin phosphatase. The major physiological functions of Rho/Rho-kinase cascade include contraction, proliferation and migration in cells.There are some excellent reviews about Rho/Rho-kinase signal pathway, most of which focus on the specific proteins of the pathway including some upstream regulators and its final effects. But few articles cover signal pathways that can activate the signaling concerned, and/or the pathways that Rho/Rho-kinase can exactly activate.This review hence highlights the two questions after a profound survey of published literatures. Rho/Rho-kinase can exert positive feedback with just another kinase/signal transducers and activator of transcription, receptor tyrosine kinase signal pathways, even reactive oxygen species, which seem to comprise certain signal loops. The authors also presume, accordingly, that the positive feedback suggests a possible reason for exacerbation of some kind of inflammatory diseases including asthma, rheumatoid arthritis, multiple sclerosis, atherosclerosis, etc. This essay, therefore, provides a new angle of view for the therapy of these kinds of diseases.

The aim of this study was to demonstrate that handgrip strength test can discriminate the presence/absence of asthma and between intermittent and moderate persistent asthma in children.140 children (70 healthy and 70 with asthma) completed the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and performed the handgrip strength test. Forty-eight hours later, subjects performed spirometry.The results showed Handgrip strength was significantly lower (p<0.001) in children with asthma compared with healthy ones. There were also significant differences (p=0.024) according to the severity of the disease; children with moderate persistent asthma performed worse than children with intermittent asthma. Binary logistic regression analysis and ROC curve analysis revealed that the result in handgrip strength test was a predictive factor for asthma (cut-off at 16.84 kg) and for severity of pathology (cut-off at 15.06 kg).Handgrip strength was reduced in children with asthma. Handgrip strength was positively associated with lung capacity and quality of life. The fact that the handgrip strength test was able to discriminate between presence/absence of asthma and between intermittent and moderate persistent asthma in children suggested that this test could be used as a complementary tool in the monitoring of asthma in daily clinical practice.

Concerns have been raised about the adverse impact of dusty air pollution (DAP) on human health. The aim of this study was to find the association between dusty air pollution based on air quality index (AQI) and the risk of allergic diseases in southwestern provinces of Iran, with assessing cytokine profiles and lymphocyte immunophenotypes.In this case control study 148 individuals participated. The sampling was done in hazardous condition (AQI>300) as the case and clean air (AQI<50) as the control. We measured cytokine production by using ELISA method and phenotypes of T-lymphocytes (CD4+and CD8+), CD19+B-lymphocytes, CD25+, CD4+CD25+cells by FACSort flow cytometer.The mean serum level of IL-4 (33.4±2.9vs 0.85±0.65 pg/dl) and IL-13 (15.1±4.4 vs. 0.12±0.7 pg/dl) in the subjects exposed to ambient DAP was increased significantly compared to the individuals in the clean air condition. Also, CD19+B-lymphocytes (12.6±4.9 vs 8.9±3.2%) and CD4+CD25+cell count (13.6±4.6 vs 7.7±3.8%) in peripheral blood were increased significantly in subjects exposed to ambient DAP compared with the controls.The result of our study suggested that ambient DAP affected immune system in a way that might lead to allergic diseases in the population.

Interleukin (IL) -25, a cytokine of IL-17 family, can activate p38 Mitogen-Activated Protein kinases (MAPK) and Nuclear Factor (NF) -c B pathways to propagate Th2 responses.The allergic rhinitis mouse model was established by stimulating BALB/c mouse with ovalbumin (OVA). Then we detected expression of IL-25 and downstream p38MAPK and NF-cB.The expression of IL-25, p38MAPK and NF-cB were detected in the OVA-induced allergic rhinitis mouse model. The allergic parameters, such as allergic symptoms, serum OVA-specific immunoglobulin E (IgE) levels and eosinophil infiltration in the nasal mucosa were compared between OVA group and control group.OVA-induced mice displayed significantly higher allergic responses compared with the saline control group. OVA induced mice demonstrated more allergic symptoms, higher serum OVA-specific IgE levels and eosinophil infiltrations. The increased expression of IL-25, p38MAPK and NF-cB immunoreactivity were detected in epidermal cells in the OVA group. The mRNA measurement of IL-25, p38MAPK and NF-cB showed the same result.IL-25 enhances the OVA-induced allergic rhinitis by activating p38MAPK and NF-cB pathways.

Bronchial asthma is the common chronic inflammatory disease and is characterized by chronic airway inflammation, airway remodeling, and airway hyperreactivity (AHR). Aim of this study was to investigate the effects of mitochondrial ATP-sensitive potassium channels (MitoKATP) on the proliferation and secretion of human airway smooth muscle cells (HASMCs). HASMCs were treated with the serum from asthmatic patients to establish HASMCs asthma model of passive sensitization. Rhodamine 123 (R-123) and 2, 7-dichloro-dihydrofluorescein diacetate (DCFH-DA) fluorescence staining were used to detect mitochondrial membrane potential (Δ ym) and the content of reactive oxygen species (ROS) in the cells, respectively.The cell counting was used to detect cell proliferation, and RT-PCR was used to detect the expression of TGF-b1 mRNA.In the normal+Diazoxide group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-b1 expression were enhanced, compared with the normal control group (p<0.05). There were no significant differences between the normal+5-hydroxydecanoate (5-HD) group and the normal control group. In the asthma model control group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-b1 expression were enhanced, compared with normal control group, (p<0.05). The aforementioned indices were enhanced in the asthma model+ Diazoxide group, when compared with the asthma model control group, whereas these indices were attenuated in the asthma model+5-HD group, when compared with the asthma model control group (p<0.05).In conclusion, asthma could activate MitoKATP channels in HASMCs, promote HASMC proliferation and TGF-b1 expression.

Mannose-binding lectin (MBL) is a Ca+2 -dependent collagenous lectin, that is produced by liver and mediates innate immune responses by opsonization of pathogens. The serum level of MBL varies widely among healthy individuals, ranging from 0.05m g/ml (or lower) to over 5m g/ml, mainly depending on genetic variations.This study has examined promoter and exon 1 of mbl2 genotype among 117 Iranian healthy blood donors. MBL Single Nucleotide Polymorphisms (SNPs) were genotyped using polymerase chain reaction (PCR), and serum levels of MBL were quantified using a double antibody enzyme linked immunosorbent assay (ELISA).Results of this study showed that there are two promoter polymorphisms at -550 (H/L variants) and -221 (Y/X variants) positions, and three polymorphisms in exon 1 at codon 52 (D Allele), 54 (B Allele), and 57 (C Allele) in this population. B allele was significantly correlated with the lowest serum MBL level. Our results also showed that the most frequent genotype was HYA/LXA, and the genotype that associated with the highest serum level of MBL was HYA/HYA. The genotype that causes lowest MBL production in Iranian population was LYB/LXA.These results showed some differences compared to that of the other populations. To verfiy the originality of these differences we may need to extend the study to a larger samples of respective populations; meanwhile the importance of a new mutation, nucleotide 101 of MBL2 exon1, reported in the current study should be taken in considerations in terms of its possible pathobiological effects in following studies.

The role of transforming growth factor (TGF) b1, interferon (IFN) -g, interleukin (IL) -2, IL-3, and IL-6 in the pathogenesis of Alzheimer’s Disease (AD) has long been reported in literature. In this case-control study, the concentrations of these cytokines in altered T lymphocytes, as well as serum vitamin B12, have been compared in terms of factors such as, age, the clinical course and the patients’ disease risk.40 patients who met the DSM-IV-TR criteria of AD were selected and an age- and gendermatched control group was recruited. The participants’ cognitive performance was measured according to the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and Clinical Dementia Ratio (CDR). The levels of cytokines were measured in supernatants of lymphocytes culture, using assays of ELISA and atomic absorption.Higher levels of IL-6 and IFN-g were found more in the altered T lymphocytes of the AD patients rather than in the control individuals. Furthermore, a marginal significant difference was found between the TGF-b levels of the two study groups. Regression analysis of CDR score and cytokines showed the inverse significant correlation between CDR score and IFN-g levels. Furthermore, the relation between MMSE scores and IFN-g was significant, meaning that by increasing MMSE score, IFN-g level was significantly increased.This study suggests that the levels of IL-6 and IFN-g are significantly increased in altered T lymphocytes of AD patients, as compared to those who are not inflicted with AD, and that they are related to the patient’s age. Also, IFN-g is related to the severity stage of the AD.

C-C motif chemokine 22 (CCL22) C16A genetic variation (rs4359426) and C-Cchemokine receptor type 4 (CCR4) C1014T variation (rs2228428) have been suggested to affect the expression level of the cognate proteins. Here we tried to investigate the plausible association of these polymorphisms with development of colorectal cancer.165 patients with colorectal adenocarcinoma (age 54.4±13.4) and 150 age- and sexmatched healthy individuals were enrolled. Genotyping was performed by PCR-RFLP methods. Results indicated the frequency of 16A allele in CCL22 gene to be 31.330 (9.4%) and 33.300 (11%) in patients and controls, respectively (p=0.59). The frequencies of CC, CA, and AA genotypes at this locus were not significantly different between patients and controls (135.165; 81.8%, 29/165; 17.6%, 1.165; 0.6% in the patients and 121.150; 80.1%, 25.150; 16.6% and 4.150; 2.6% in the control group, p= 0.34). At the locus 1014 in CCR4, T allele was observed with the frequency of 107.330 (32.4%) and 83.300 (27.7%) in patients and controls, respectively (p=0.22).Analyses indicated no significant differences in the frequencies of CC, CT and TT genotypes at this locus between patients and controls (77.165; 46.7%, 69/165; 41.8% and 19.165; 11.5%; versus 83.150; 55.0%, 51.150; 33.8% and 16.150; 10.6%, respectively, p=0.29). The presence of individual genotypes was not associated with clinicopathological characteristics of the disease, including tumor size, tumor grade and LN involvement (all with p>0.05).These findings collectively suggested that CCR4 C1014T and CCL22 C16A genetic variations were neither associated with the risk, nor with the progression of colorectal cancer in Iranian population.

Mast cells are related to certain gastrointestinal complaints. Mast cell density has not been studied in cardio-esophageal region to the best of our knowledge. In this study we wanted to obtain an estimate of mast cell density in this region and compare it with mast cell density in antrum.From April 2007 till March 2010, we chose children (<14 years old) who underwent upper endoscopy and from whom the taken biopsy was stated to be from lower third of esophagus, but in microscopic examination either cardio- esophageal mucosa or only cardiac mucosa was seen. Mast cells were counted by Giemsa stain at ×1000 magnification in 10 fields.71 children (<14 years old) were included in this study of which, 63.4% (n=45) were female and 36.6% (n=26) were male. The mean age of patients was 7.20±4.21 years (range: 0.2-14 years). The most common clinical manifestations were recurrent abdominal pain (64.8%) and vomiting (23.9%) followed by symptoms of gastro-esophageal reflux disorder, poor weight gain, hematemesis and dysphagia.The mean mast cell density in the cardiac mucosa was 33.41±32.75 in 0.25 mm2 (range: 0-155), which was two times of that in antral mucosa. We found a significant but weak positive correlation at the 0.05 level between mast cell density of cardiac mucosa and the antrum.Higher mast cell counts were seen in cardiac mucosa in this study. Significant positive correlation between mast cell density of cardiac mucosa and the antrum could hint to a single underlying etiology for the inflammatory process in gastro- esophageal junction and gastric mucosa.

We describe, the first case of phenobarbital-induced DRESS syndrome presenting as a lichenoid eruption.A 49-year-old man had received phenobarbital for a cerebral metastasis. Twenty-five days later, he developed a purplish skin eruption, odynophagia, oral mucosal erosion and fever. Physical examination revealed a cervical lymphadenopathy and facial edema associated to a diffuse violaceous maculo-papular itchy rash. Laboratory findings showed a 1200/mm3 eosinophil’s cell count. Alanine aminotransferase was 169 IU/l. Lactate dehydrogenase and creatinine phosphokinase were at 768 and 90 IU/l, respectively. All symptoms resolved completely five weeks after phenobarbital withdrawal. Few days later, the patient died because of a cardio-respiratory arrest.

Henoch-Schonlein purpura nephritis is a small vessel vasculitis that can involve not only the kidneys but also the gut, joints and skin, to varying extents. In contrast, IgA nephropathy is recognized as a renallimited, non-systemic disease. However, Henoch-Schonlein purpura nephritis and IgA nephropathy share many immunological, histological and clinical features. Indeed, IgA nephropathy and Henoch-Schonlein purpura nephritis are thought to be related diseases.