1,721,002 research outputs found
Nutlin-3 differentially modulates miRNA34a and miRNA181 versus miR26a and miR155 in p53 proficient and p53 deficient B chronic lymphocytic leukemia (B-CLL) samples
No full textThe small molecule inhibitor of the MDM2/p53 interaction Nutlin-3 is a promising anti-cancer agent, which exhibits activity against a variety of cancers, including acute myeloid leukemia (AML). Previous studies have shown that Nutlin-3 variably induces apoptosis and cell cycle arrest in cancer cells while it shows low/absent cytotoxicity in normal cells. However, the reason for the selective pro-apoptotic activity in cancer cells with respect to normal counterparts is incompletely understood. In this study, we have compared the induction of several known target genes of p53 in two p53wild-type AML cell lines, OCI-AML3 and MOLM, in comparison with primary normal peripheral blood mononuclear cells (PBMC). Among several p53-target genes activated both in AML cell lines and normal PBMC (BBC3, BAX, MDM2, FAS, CDKN1A, GDF15, GADD45A, TNFRSF10B, TP53I3/PIG3), only TP53I3/PIG3 was selectively activated in MOLM and OCI-AML3, but not in PBMC. The important role of TP53I3/PIG3 in mediating the apoptotic activity of Nutlin-3 was underlined by knock-down experiments with siRNA specific for TP53I3/PIG3, which resulted in a significant decrease in the pro-apoptotic activity of Nutlin-3
Presence of CTAK/CCL27, MCP-3/CCL7 and LIF in human colostrum and breast milk
No full textHuman colostrum and breast milk are known to contain high levels of cytokines and chemokines, which are thought to contribute to the development of the newborn. The aim of this study was to investigate the difference in the presence and levels of 21 soluble cytokines and chemokines in paired samples of human colostrum (day 2 after delivery) and breast milk (day 4-5 after delivery) by using the multiplex technology. Of the 21 cytokine investigated in 10 pairs of samples, only β-NGF was absent in both colostrum and milk, while INF-α2, SCF and TNF-β were present in colostrum but not in human milk. As a general rule, colostrum contained higher concentrations of cytokines and chemokines with respect to breast milk. The majority of cytokines, detected in colostrum alone or in colostrum and human milk (IL-1α, IL-2Rα, IL-3, IL-16, IL-18, GRO-α, HGF, IFN-α2, M-CSF, MIF, MIG, TNF-β, SDF-1α, TRAIL) have been described in previous studies, while for the first time we describe the presence of additional cytokines either in colostrum alone (SCF) or in both colostrum and breast milk (CTAK/CCL27, MCP-3/CCL7, LIF). Our data confirm and expand previous studies showing that some cytokines/chemokines, which might contribute to the development of the gastro-intestinal and nervous systems, are overexpressed in human colostrum and breast milk, and might contribute to the development of these system
Analysis of anti-C1q antibodies in normal and pathological pregnancies
No full textAnalysis of anti-C1q antibodies in normal and pathological pregnancies
C. Agostinis1, A. Mangogna2, O. Radillo1, G. Ricci1, R. Bulla2.
1. Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137, Trieste, Italy;
2. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy.
PROBLEM
C1q, the recognition molecule of the classical pathway of the complement system plays foundamental roles in pregnancy. C1q has been shown to promote trophoblast endovascular and interstitial invasion and is involved in the clearance of immune complexes and apoptotic bodies. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure.
This molecule can be also the target of an antibody response: anti‐C1q antibodies are present in several infectious and autoimmune diseases. The presence of these auto-antibodies has been detected also in 2 to 8% of the general population.
The aim of this study was to evaluate the presence and the circulating levels of anti-C1q Ab in pre-eclamptic (PE) patients compared to healthy pregnant women.
METHOD
Levels of anti‐C1q antibodies were analyzed by ELISA in PE and control sera obtained in the first and third trimester of pregnancy.
RESULTS
Anti-C1q antibodies were detected in both normal and PE sera. Higher levels of these antibodies were present in the first trimester compared to term normal pregnant sera. Early onset PE patients showed higher levels of anti-C1q antibodies compared to late onset PE patients.
CONCLUSION
Anti-C1q antibody levels increased during the first trimester of pregnancy. The level of these antibodies was higher in the sera of some early onset PE patients. These data indicates a possible role of anti-C1q antibodies in the control of pregnancy and in the pathogenesis of PE. The role played by these antibodies at foeto-maternal interface requires further investigation
Latent viral infections in young patients with inflammatory diseases treated with biological agents: Prevalence of JC virus genotype 2.
No full textTreatment with biological drugs is associated with increased susceptibility to viral infections. Reactivation of JC virus (JCV) and human cytomegalovirus (HCMV) in adults after therapy has been documented. The long-term effects of biological and conventional therapy on human herpesviruses and polyomaviruses infections in young patients were assessed. One hundred eighty-six samples [urine, serum, and blood cells (PBMCs)] from 62 patients (15.8 ± 6.2 years old) with Crohn's disease, ulcerative rectocolitis or juvenile rheumatoid arthritis treated with immunotherapy or conventional therapy for over 12 months were tested by real time PCR. One hundred twenty-four samples (urine and blood) from 62 matched healthy volunteers (13.8 ± 8.6 years old) were included as controls. Sequencing of the JCV viral protein 1 (VP1) and transcriptional control region (TCR) was performed. Herpes simplex virus 1/2 and varicella zoster virus genomes were not detected in any patients, whereas Epstein-Barr virus, HCMV, and human herpesvirus-6 genomes were detected in 4.8%, 3.2%, and 1.6% of the patients, respectively. JCV was detected in 22.6% (14/62) of urine samples from patients and in 8% (5/62) from controls, in 50% (7/14) of sera from patients shedding JCV, and in 71.4% (5/7) of matched PBMCs. There was a significant association between infliximab treatment and excretion of JCV genotype 2. Subclinical infection/reactivation of JCV genotype 2 in young patients during infliximab therapy was demonstrated. Conversely, increased susceptibility to herpesviruses infection was not shown. Future studies are warranted to investigate the effects of JCV reactivation on the health of young patients treated with infliximab
C1q is responsible of the anti-inflammatory behavior of decidual endothelial cells
No full textPROBLEM: Endothelial cells (ECs), although similar in function and morphology, represent an heterogeneous population of cells in terms of secretion of inflammatory mediators, modulation of adhesion molecules, leakiness and pro-coagulant activity and play a fundamental role in the control of the inflammatory response. Excessive inflammation at foetal-maternal interface is thought to be a key contributor in a compromised pregnancy. Intrauterine infections have been associated with pregnancy complications such as preterm labor, intrauterine growth restriction and preeclampsia.
We demonstrated that decidual endothelial cells (DECs) compared to ECs isolated from adult skin (ADMECs) are ipo-responsive to the pro-inflammatory stimulus LPS for the expression of adhesion molecules and cytokines secretion. We showed also that DECs express lower level of TLR4, MD2 and MyD88 compared to ADMECs and this may be important for the control of the inflammatory response at foeto-maternal interface.
We have previously shown that DECs acquired the ability to synthesize C1q during pregnancy which is to a large extent localized on the cell surface. Since it has been demonstrated that C1q suppressed LPS-induced IL-12p40 production in bone marrow-derived DC (BMDC) we hypothesised that C1q can play a role in the control of DECs response to LPS.
METHODS: We investigated the expression of TLR4, MD-2, and MyD88 in ADMECs previously incubated for two hours with C1q in cells stimulated or not with LPS by Real Time PCR, Western blotting and cytofluorimetric analysis.
RESULTS: Our results showed that C1q affects mRNA expression of TLR4, MD-2, and MyD88 both in resting and in stimulated cells,
CONCLUSION: The presence of C1q at foeto maternal interface may be responsible of the control of inflammation during pregnancy
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