[Study on the relationship of the haplotypes of programmed cell death 1 gene and ultraviolet history with systemic lupus erythematosus].

OBJECTIVE: To investigate the relationship of gene polymorphisms of programmed cell death 1 gene (PDCD1) and ultraviolet history with systemic lupus erythematosus (SLE) among the Han population in the southern region of yangtze river in China. METHODS: With a case control design, a total of 159 SLE cases and 159 controls were enrolled in this study, and single nucleotide polymorphisms (SNPs) of the PDCD1 gene were determined by PCR-restriction fragment length polymorphism (RFLP). With the aid of the logistic regression model, the effect of gene polymorphism, environmental factor and the interaction between gene and environment were fitted under the recessive, dominant, additive and codominant mode, respectively. RESULTS: Three models were screened as the optimal models under the additive mode and one model under the dominant mode, according to the lowest value of Akaike's Information Criteria (AIC). After the control of age and gender, it was found that the frequency of ultraviolet exposure was higher in cases than in controls with significant difference under all models (P<0.05). For the haplotypes composed of the alleles of PD1.2, PD1.5 and PD1.6, there was significantly higher frequency of G-T-A haplotype (0.1196 vs 0.0363) and lower frequency of A-C-A haplotype (0.4746 vs 0.5399) in cases than that in controls (P<0.05) under the additive mode, and the G-T-A haplotype was associated with an increased risk for SLE (OR=4.319), while A-C-A haplotype was shown as a protective factor for SLE (OR=0.571). Moreover, interaction between A-C-G haplotype and ultraviolet exposure, which was related to an increased risk for SLE (beta5=1.182, Z=2.2898, P<0.05, OR=3.261), was also found under this mode. Additionally, the frequency of G-C-G haplotype was higher in cases than that in controls (0.1287 vs 0.0361) under the dominant mode with statistically significant difference (P<0.05, OR=4.332). CONCLUSION: Authors' results indicate that ultraviolet exposure, G-T-A or G-C-G haplotype and interaction between A-C-G and ultraviolet exposure may be associated with genetic susceptibility to SLE in Han population in the southern region of yangtze river in China under certain genetic modes.

[Interactions between susceptible genes and risk environmental factors in Chinese females with systemic lupus erythematosus].

OBJECTIVE: To explore the interactions of gene polymorphisms of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PDCD-1) with risk environmental factors in individuals with systemic lupus erythematosus (SLE) from Han nationality female population in South of Changjiang River region of China. METHODS: With a case-only design, a total of 258 cases were enrolled in this study, and single nucleotide polymorphisms (SNPs) of the PDCD-1 and CTLA-4 genes were determined by means of PCR-RFLP. With the aid of Poisson loglinear mode, interactions between gene-gene and gene-environment were fitted under the dominant, recessive, additive and multiple models, respectively. RESULTS: It was found that interaction existed between GG genotype of PD1.6 and UV history under separate inherent models of the recessive mode (OR = 3.714, 95%CI: 1.235 - 11.179) and additive mode (OR = 3.199, 95%CI: 1.023 - 10.004). For CTLA-4 locus, there existed interactions between TT/TC genotype of -1722T-->C and UV history under the dominant model (OR = 4.874, 95%CI: 1.119 - 21.242), and interaction between T allele and UV history was also found under the multiple model (OR = 1.470, 95%CI: 1.047 - 2.065). While, under the additive mode for CTLA-4, it was found that interactions existed between TT genotype of -1722T-->C and UV history (OR = 4.744, 95%CI: 1.037 - 21.737), as well as between TC genotype of -1722T-->C and UV history (OR = 4.973, 95%CI: 1.110 - 22.287). CONCLUSION: The interactions between UV history and polymorphisms of CTLA-4 and PDCD-1 gene for SLE were observed, which indicates that there may be association of their interactions with the development of SLE in Han nationality females population in the south regions of Changjiang River in China.

[Tripterine inhibits all-trans retinoic acid-caused adhesion between leukemia cells and endothelial cells].

OBJECTIVE: Increasing of adhesion between leukemia cells and endothelial cells during all-trans retinoic acid (ATRA) treatment plays an important role in retinoic acid syndrome. This work observed the effects of tripterine on this ATRA-caused increasing in adhesion. METHODS: The effects of tripterine on ATRA-induced expressions of adhesive molecules in acute promyelocytic leukemia cell line NB4 and human umbilical vascular endothelial cells (HUVEC) were detected by flow cytometry. The effects of tripterine on adhesion between ATRA-treated NB4 and HUVEC were determined by adhesive assays. RESULTS: ATRA caused remarkable elevation of intercellular adhesion molecule-1 (ICAM-1) in NB4 cells, which could be significantly reduced by tripterine (P<0.01). The expressions of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and ICAM-1 in HUVEC were elevated by conditioned medium from ATRA-induced NB4 (ATRA-NB4-CM) (P<0.01), and inhibited by tripterine with inhibition rates being 25.3%, 42.4% and 61.0% respectively. ATRA increased the adhesion between NB4 and HUVEC, which was reversed completely by tripterine. CONCLUSION: Tripterine can inhibit ATRA-caused adhesion between leukemia cells and endothelial cells, and it might be a potential agent for treating retinoic acid syndrome.

Tripterine inhibits the expression of adhesion molecules in activated endothelial cells.

Cell adhesion molecules (CAM) expressed by vascular endothelium in response to cytokine stimulation play a key role in leukocyte adhesion to endothelium during the inflammatory response. Tripterine, a chemical compound of the Chinese plant Tripterygium wilfordii Hook f, displays anti-inflammatory properties in several animal models. However, mechanisms of its action are poorly understood. In the present study, we show that in inflammatory conditions, mimicked by tumor necrosis factor alpha (TNF-alpha) stimulation, pretreatment for 6 h with tripterine at nontoxic concentrations of 20-200 nM inhibits the expression of E-selectin, vascular cell adhesion molecule (CAM)-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. Tripterine (200 nM) almost completely inhibits expression of VCAM-1 [50% inhibitory concentration (IC50) = 52 nM] and ICAM-1 (IC50 = 51 nM) and 73% of E-selectin (IC50 = 94 nM). This inhibition effect is prominent, compared with that of dexamethasone, ibuprofen, methotrexate, or probucol, which revealed a much weaker inhibition at doses as high as 1 mM. Effects on endothelial CAM of other proinflammatory cytokines, such as interleukin-1beta and interferon-gamma, were also inhibited significantly by tripterine. Moreover, significant inhibition was equally observable in postincubation experiments. In addition, tripterine inhibited adhesion of human monocytes and T lymphocytes to TNF-alpha-stimulated HUVEC. Finally, tripterine inhibited TNF-alpha-driven CAM mRNA transcription and nuclear factor-kappaB nuclear (NF-kappaB) translocation. Hence, we describe a new mechanism of tripterine's anti-inflammatory action obtained at nanomolar concentrations, owing to the negative regulation of cytokine-induced adhesion molecule expression and adhesiveness in human endothelium.