Comparison of immune regulatory factors in acute and chronic lesions of cutaneous leishmaniasis due to Leishmania major.

BACKGROUND: Adaptive immune response is an important factor in the healing process and development of protection in cutaneous leishmaniasis (CL). Little information is available in human CL about the importance of the balance between effector and regulatory immune responses. Therefore, the aim of this study was to asses messenger ribonucleic acid (mRNA) expression of interleukin-10 (IL-10), IL-4, transforming growth factor-ß1 (TGF-ß1), interferon-g (IFN-γ), and forkhead box P3 (Foxp3) (as a marker of regulatory T cells) in acute and chronic CL lesions caused by Leishmania major compared with normal skin samples. MATERIALS AND METHODS: Thirty biopsies were obtained from CL patients with acute lesions (AL, n = 13), chronic lesions (CH, n = 11) and healthy volunteers (n = 6). Relative expressions of target genes were determined by means of reverse transcription real time polymerase chain reaction and were compared with the controls. RESULTS: Expression of Foxp3, IL-4, and IFN-γ were significantly more in CH than AL group of patients (Foxp3: Median 0.48, inter-quartile range 0.32-0.76 [arbitrary units] for AL, and 0.97 (0.75-1.30) for CH, P = 0.006; IFN-γ: 45.98 (33.39-173.48) for AL, and 200.53 (97.49-361.76) for CH, P = 0.023; IL-4: 0.49 (0.34-2.16) for AL, and 2.14 (1.30-7.11) for CH, P = 0.021). Expression of TGF-ß was not significantly different between groups. CONCLUSION: The results indicate that IL-4 secretion at the site of L. major infection rather than low IFN-γ production might have a role in prolongation of disease. Despite a moderate increase of Foxp3 expression in chronic lesions, function of Tregs in persistent infection is not clear.

Association between heme oxygenase-1 gene promoter polymorphisms and metabolic syndrome in Iranians.

Heme oxygenase-1 (HO-1) which is a rate-limiting enzyme in heme degradation processes shows a dinucleotide GT repeat in the promoter that alters the level of gene transcription. This study is aimed to assess the association of HO-1 gene promoter polymorphism and metabolic syndrome (MetS). A hundred and fifty two individuals, who were followed in Isfahan Cohort Study since 2001, were enrolled in this study. They consisted of 78 MetS patients and 74 controls without MetS. Blood samples were obtained from all participants and after extracting the genomic DNA, promoter sequence was determined by PCR-based genotyping. The serum levels of iron, ferritin and bilirubin were also measured in all subjects. The proportion of short and long allele frequency did not significantly differ in patients with metabolic syndrome compared to control group. In conclusion, the results showed that there is no significant difference between two groups in (GT)n repeat of HO-1 gene promoter. These findings suggest the insignificant role of genetic risk factors compared to environmental risk factors in the development of MetS.

Synergistic effects of genetic polymorphism and air pollution on markers of endothelial dysfunction in children.

BACKGROUND: This study aims to determine the association of some genetic polymorphisms in the relationship of air pollutants on the serum levels of thrombomodulin (TM) and tissue factor (TF) in a population-based sample of children and adolescents. MATERIALS AND METHODS: This cross-sectional study was conducted among 110 participants (52.8% girls) with a mean age of 12.7 + 2.3 years, in Isfahan, Iran. Genotypes of TM G33-A and + 5466A > G polymorphisms were determined by the polymerase chain reaction - restriction length fragment polymorphism method (PCR-RFLP). The enzyme-linked immunosorbent assay (ELISA) was used for measurement of serum TM and TF. RESULTS: THE FOLLOWING GENOTYPES WERE IDENTIFIED FOR TM: GG in 69.2%, GA in27.2%, and AA in 3.6% of the participants. Considering TF, 108 participants were homozygous for the + 5466A allele, and two subjects had + 5466AG genotype. The mean pollution standards index (PSI) value was at a moderate level; the mean particulate matter measured up to 10 µm (PM(10)); and ozone (O(3)), nitrogen dioxide, and sulfur dioxide were considerably high. The mean serum TF and TM levels were not significantly different among the participants with the aforementioned genotypes. Among participants exposed to high quartiles of O(3), PM(10), and PSI, the TM-33G / A polymorphism (GA + AA genotype) increased the Odds ratio (OR) of the low serum TM level. There was no statistically significant association in the areas of low pollution. CONCLUSION: The findings of our study support the synergistic effect of the TM-33G / A polymorphism and air pollutants on factors associated with the onset of the atherosclerosis. This might be confirmatory evidence for gene-environment interaction, and related effects on atherogenesis from early life.

Regulatory T-cell profile in early and late lesions of cutaneous leishmaniasis due to Leishmania major.

CONTEXT: Cutaneous leishmaniasis (CL) is a public health problem in several endemic countries. Recent studies on mouse model and also a few clinical experiments showed that the type of immune response generated at the site of infection and especially balance between regulatory and effector T-cells determines the outcome of the disease toward self-limiting or long-lasting lesions. AIMS: The aim of this study was to evaluate the role of natural regulatory T cells (nTregs) in early and late cutaneous lesions of human Leishmania major (L. major) infection. SETTINGS AND DESIGN: Skin biopsies were collected from parasitologically proven lesions of 28 CL patients, divided into two groups of early and late lesions. The causative agents were identified to be L. major. MATERIALS AND METHODS: Quantitative real-time reverse transcription polymerase chain reaction (PCR) and immunofluorescent staining of biopsies were used to assess the Foxp3 mRNA expression and frequency of nTregs in two groups. Mann-Whitney U test was used to determine the significance of deference between the two groups. RESULTS: Mean relative expressions of Foxp3 mRNA were 0.53 ± 0.23 and 1.26 ± 0.99 in early and late lesions, respectively, which was significantly upper in chronic lesions (P = 0.007). Parallel results were obtained in tissue staining method. CONCLUSIONS: Increased in gene expression and protein staining of nTreg markers in chronic biopsy samples indicates a role for these cells in chronic L. major induced leishmaniasis and supports the effectiveness of regulatory T cell-based immunotherapy for treatment of chronic CL.

Relationship of lipoprotein lipase gene variants and fasting triglyceride levels in a pediatric population: The CASPIAN-III study.

BACKGROUND: Lipoprotein lipase (LPL) is one of the major enzymes responsible for the hydrolysis of triglyceride (TG)-rich lipoprotein. The effects of LPL polymorphisms on serum TG are inconsistent among different populations. OBJECTIVES: This study aims to assess the TG serum concentration and distributions of three LPL single nucleotide polymorphisms (SNPs), namely D9N, HINDIII and S447X, in a nationally representative sample of Iranian adolescents. MATERIAL AND METHODS: We studied the associations between SNP genotypes and TG levels in a nationally representative sample of Iranian adolescents. Genotyping was performed in 750 randomly selected participants. We compared the genotypes according to different TG levels. RESULTS: This study comprised 746 participants, with mean ± SD age of 14.6 ± 2.5 years. The distribution of genotypes of D9N and S447X were not significantly different according to TG levels. Regarding the HINDIII polymorphism, the distribution of GG, GT, and TT genotypes were significantly different in participants with low, borderline-high, and elevated TG (p = 0.02, 0.03, and 0.01, respectively). The mean TG was not significantly different according to the genotype distribution. CONCLUSIONS: In this study, most of the LPL gene variants were not significantly different in adolescents with normal and elevated TG, and the mean TG was not different in participants with various genotypes. As the first evidence from the pediatric population of the region of the Middle East and North Africa (MENA), these results might be used in international comparisons. Our findings might suggest that the high prevalence of hypertriglyceridemia in Iranian adolescents is more likely to be a result of lifestyle rather than genetic factors.