Transforming growth factor beta-1 (TGF-ß1) gene single nucleotide polymorphisms (SNPs) and susceptibility to pre-eclampsia in Iranian women: A case-control study.

OBJECTIVES: Pre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-ß1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-ß polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-ß1 and serum level of this cytokine in PE patients and controls. DESIGN AND METHODS: In this study the polymorphisms of the TGF-ß1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-ß1 was determined by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: At positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P=0.3 and P=0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P=0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P=0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-ß1 level was significantly higher (62.73ng/ml) in PE patients compared with pregnant (47.01ng/ml) and non-pregnant (40.68ng/ml) control groups (P=0.0001). CONCLUSIONS: The results of this study suggest that TGF-ß1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia.

Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis.

BACKGROUND AND PURPOSE: Some functional limitations and economic burden of therapeutic antibodies indicated that introducing of alternative therapeutic compounds with same or different mechanism of action could be worthwhile. In this regard small-molecule antagonists can have a wide range of impacts, so in this research, we examine the prophylactic effects of BIO-1211 [Very Late Antigen-4 (VLA4) blocker], in experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in comparison with commercial available medicine, Natalizumab (NTZ)]. METHODS: EAE was induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein (MOG35-55) in 8-week-old C57BL/6 mice. During EAE induction, mice were separated to distinct groups and provided either BIO-1211 (5 and 10 mg/kg) or NTZ (5 mg/kg) and co-administration of these two compounds. After 21 days, neuro-inflammatory responses were analyzed using qRT-PCR, western blot, and ELISA methods. Pervade of immune cells to brain was examined by Evans blue staining and immunohistochemistry (IHC) analysis of specific markers of microglia/monocytes (CD11b) and leukocytes (CD45). RESULTS: Targeted disruption of VLA4/VCAM1 interactions, by BIO-1211 agonist in mice, results in reduced cytokines expression, leukocyte trafficking, and inhibition of inflammatory responses in EAE (p < 0.01) in a dose-independent manner (data not shown). Mice treated with both BIO-1211 and NTZ exhibited a considerable depletion in the EAE clinical score, which correlated with decreased expression of TNF-α, IL-17, IFN-γ and pervade of CD11b(+) and CD45(+) cells into the cerebral cortex. CONCLUSION: Our results indicated that BIO12-11 compound would be an useful tool to further understand the biological roles of VLA4/VCAM1 interactions, and could also be considered as EAE-suppressing agent.

Elevated expression of NLRP1 and IPAF are related to oral pemphigus vulgaris pathogenesis.

Oral pemphigus vulgaris (PV) is a rare blistering disorder of the skin and mucous membranes in the mouth. Inflammasome serves as a molecular platform that mediates the autoactivation of caspase-1, which cleaves the pro-forms of IL-1ß and IL-18 to active forms. Therefore, the main aim of this study was to evaluate the messenger RNA (mRNA) levels of NOD-like receptor-related protein (NLRP)1, NLRP3, and IPAF in the PBMCs of PV patients to determine their effect in PV pathogenesis. This study was designed as a cross-sectional study. We studied mRNA levels of three types of inflammasomes including NLRP1, NLRP3, and IPAF in 43 oral PV patients and 40 healthy controls by real-time PCR technique. Results were analyzed by SPSS software package version 18. Here, we showed that the mRNA levels of NLRP1 and IPAF in patients with active PV remarkably increased compared to those in healthy controls. However, the mRNA level of NLRP3 in PBMC of PV patients was similar to that of the control group. We showed important and emerging relationship of NLRP1 and IPAF mRNAs with PV disease progression. We hypothesize that NLRP1 and IPAF with cytokine activity of IL-1ß are involved in the inflammation in PV patients.

Promoter region polymorphisms in the transforming growth factor beta-1 (TGFß1) gene and serum TGFß1 concentration in preeclamptic and control Iranian women.

Preeclampsia (PE) is a pregnancy associated disorder characterized by hypertension and proteinuria, which causes neonatal and maternal morbidity and mortality. The Th1/Th2 cytokine paradigm of the immune adaptation in pregnancy is now expanded to include Th1/Th2/Th17 and regulatory T (Treg) cells. Among cytokines, TGFß1 has properties that justify evaluation of its role in PE etiopathology. In this investigation the polymorphisms of the TGFß1 gene at promoter region, positions -800G→A and -509C→T, were studied in 142 PE and 140 normal pregnant female subjects using PCR-RFLP. Additionally, serum TGFß1 was determined by ELISA. At position -800G→A genotypes and allele frequencies showed no significant differences between PE patients (GG 73.9%; GA 21.1%; AA 4.93%) and normal control (GG 70%; GA 28.6%; AA 1.4%) women. However the AA genotype at this position was more frequent in PE patients than in the control group. At -509C→T position, genotypes and allele frequencies showed no significant differences between PE patients and control individuals. The CC genotype at -509C→T position was more prevalent in PE patients than in the control group. The mean serum TGFß1 level was significantly higher (62.14 ng/ml) in PE patients compared with pregnant and non-pregnant control groups (and 47.01 and 40.68 ng/ml, respectively). In conclusion, the promoter region polymorphisms of TGFß1 may not be associated with PE, but serum levels of this cytokine may contribute to the etiopathology of PE.