ABSTRACT
As an anti-inflammatory cytokine, interleukin-37 (IL-37) provides certain protective effects against inflammatory and autoimmune diseases. Recent reports indicate that IL-37 is expressed in foam cells of atherosclerotic plaques in both the coronary and carotid arteries of humans, suggesting the possible involvement of IL-37 in the pathogenesis and progression of atherosclerosis. Current evidence supports the protective role that IL-37 plays against atherosclerosis via the regulation of different subtypes of macrophage. Atherosclerosis was induced in apolipoprotein E -/- mice through diet, and the mice were then given IL-37 to observe patterns in the aorta plaque. Furthermore, human peripheral blood-derived monocytes were cultured for seven days to induce the differentiation of macrophages. Specifically, we observed the effect of IL-37 on oxygenated low density lipoprotein (ox-LDL)-induced macrophage polarity, in addition to conducting an expressional assay of the M1 cell markers tumor necrosis factor (TNF)-α and CD86 and the M2 marker CD206. IL-37 effectively decreased the area ratio between the aorta plaque and vascular cavity. We also observed that M1 macrophages can be induced from peripheral monocytes by ox-LDL, with significant elevation of marker molecules TNF-α and CD86. The co-stimulation of IL-37 and ox-LDL, however, inhibited the induction of M1 cells and facilitated the transformation of macrophages into M2 cells, as supported by the elevation of cell-specific marker CD206. These results indicate that IL-37 can prevent atherosclerosis by modulating macrophage polarity.
Subject(s)
Atherosclerosis/drug therapy , Interleukin-1/pharmacology , Macrophages/drug effects , Animals , Apolipoproteins E/deficiency , Apolipoproteins E/immunology , Atherosclerosis/immunology , Atherosclerosis/pathology , Cell Differentiation/drug effects , Cell Polarity/immunology , Disease Models, Animal , Foam Cells/drug effects , Foam Cells/immunology , Humans , Macrophages/immunology , Male , Mice , Mice, Knockout , Plaque, Atherosclerotic/immunology , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/prevention & control , Random Allocation , Recombinant Proteins/pharmacology , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Clopidogrel hydrogen sulfate (CHS) is a thienopyridine, which can be used to prevent cardiovascular complications alone or in combination with acetyl salicylic acid as an important antiplatelet agent. Clopidogrel benzene sulfonate (CB) is a special clopidogrel salt that can be used as a conventional drug for antiplatelet effects, but the mechanism is still unknown. This study aimed to compare the antiplatelet effects of CHS and CB in stable coronary artery disease patients. Stable coronary artery disease patients (N = 119) were randomly divided into two groups receiving CHS (N = 67) or CB (N = 52). The patients were administered the drugs (600 mg dosage) and monitored for 12 to 14 h to detect antiplatelet effects. Antiplatelet response was evaluated by the P2Y12 response unit (PRU) and P2Y12 suppression percentage. In addition, all patients' CYP2C19*2, CYP2C19*3, and CYP3A5 polymorphisms were studied. Similar clinical manifestations were observed in the two groups. No obvious difference was detected in the platelet levels of patients given CHS or CB. The antiplatelet response (PRU and P2Y12 evaluation) of the patients using CHS and CB was not significantly different. In the two groups, the CYP2C19*2 polymorphic heterozygote number and antiplatelet response were similar. CB and CHS presented similar antiplatelet effects in stable coronary artery disease patients, and there was no difference in the CYP2C19*2 heterozygous polymorphism.
Subject(s)
Aspirin/administration & dosage , Coronary Artery Disease/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Ticlopidine/analogs & derivatives , Adult , Aged , Clopidogrel , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP3A/genetics , Drug Combinations , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/chemistry , Ticlopidine/administration & dosage , Ticlopidine/chemistryABSTRACT
OBJECTIVE: PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor-associated antigen recognized by immunocytes, and it induces cytotoxic T cell-mediated responses in melanoma. PRAME is expressed in a wide variety of tumors, but in contrast with most other tumor-associated antigens, it is also expressed in leukemias. The physiologic role of PRAME remains elusive. Recently, it has found PRAME could be involved in the regulation of cell death in leukemias, but the mechanism of the function is unclear. Here, we confirm that PRAME induces leukemias cell death by regulation of S100A4/p53 signaling. MATERIALS AND METHODS: The pCDNA3-PRAME plasmid and its control were transfected with the KG-1 cells. The pCDNA3-PRAME transfected KG-1 cells were then transiently transfected with S100A4 cDNA or wt-p53 siRNA. The PRAME siRNA and its control were transfected with the K562 cells. The PRAME siRNA transfected K562 cells were then transiently transfected with S100A4 siRNA or pGMp53-Lu. PRAME, S100A4 and P53 were detected by Western blot assay in different time point. Annexin V/propidium iodide and MTT methods were used to detect apoptosis and cell survival rate. RESULTS: KG-1 cells overexpressing the PRAME gene significantly induces apoptosis and decreases proliferation in vitro, followed by down-regulation of S100A4 and up-regulation of p53. Up-regulation of S100A4 by S100A4 transfection inhibits PRAME-induced p53 up-regulation. Furthermore, up-regulation of S100A4 by S100A4 transfection or down-regulation of p53 by p53 siRNA transfection reduces apoptosis and increases proliferation in vitro. Knockdown of PRAME in K562 cells significantly increases proliferation in vitro, followed by up-regulation of S100A4 and down-regulation of p53. The downregulation of S100A4 by S100A4 siRNA transfection increased p53 expression. Furthermore, downregulation of S100A4 by S100A4 siRNA transfection or up-regulation of p53 by p53 transfection decreases proliferation in vitro. CONCLUSIONS: Our results suggest that the leukemias expressing high levels of PRAME has a favorable prognosis. PRAME promotes in vitro leukemia cells death by regulating S100A4/p53 signaling.
Subject(s)
Antigens, Neoplasm/biosynthesis , Genes, p53/physiology , Leukemia/metabolism , S100 Calcium-Binding Protein A4/physiology , Signal Transduction/physiology , Antigens, Neoplasm/genetics , Apoptosis/physiology , Cell Death/physiology , Cell Survival/drug effects , Cell Survival/physiology , Humans , K562 Cells , Leukemia/genetics , Leukemia/pathology , RNA, Small Interfering/biosynthesis , RNA, Small Interfering/geneticsABSTRACT
OBJECTIVE: To study the relationship between human papillomavirus (HPV) and pathological characteristics of the patients with infantile respiratory tract papillomas (IRP). METHOD: Thirteen cases of infantile respiratory tract papillomas tissue were analysed for Papillomavirus by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULT: The amplified products of the HPV-L1 region by PCR by using the consensus primers showed that the presence of HPV was 100 percent. Eight cases(61.5 percent) were positive for HPV6 only. Four cases (30.8 percent) were positive for HPV11 only. One case (7.7 percent) showed the presence of HPV18. None were positive for HPV16, 31, 33, 52, 58. CONCLUSION: Infantile respiratory tract papillomas are associated with HPV6, 11, 18 infection, but the subtypes of HPV are not associated with clinical pathological characteristics.
