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Receptor Downregulation (receptor + downregulation)
Selected AbstractsAnesthesia for Heart or Single or Double Lung Transplantation in the Adult PatientJOURNAL OF CARDIAC SURGERY, Issue 3 2000Paul M. Chetham M.D. Patients with end-stage cardiac dysfunction have an impaired response to ,-agonist due to receptor downregulation. These patient will have isolated left ventricular dysfunction secondary to ischemic heart disease or present with biventricular failure with or without significant pulmonary hypertension. Increasingly, more patients have undergone prior major cardiac procedures and are at risk for significant perioperative bleeding. Patients undergoing single or double lung are particularly challenging because most of these procedures are performed without the aid of cardiopulmonary bypass. The anesthesiologist must be proficient at the management of one-lung ventilation techniques and have a rational physiologic approach to the management of intraoperative hypoxemia and auto-PEEP. [source] Potential mechanisms for astrocyte-TIMP-1 downregulation in chronic inflammatory diseasesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Jessica Gardner Abstract The pathogenesis of many neurodegenerative disorders, including human immunodeficiency virus (HIV)-1 associated dementia, is exacerbated by an imbalance between matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). In the context of disease, TIMP-1 has emerged as an important multifunctional protein capable of regulating inflammation. We previously reported differential TIMP-1 expression in acute versus chronic activation of astrocytes. This study investigates possible mechanisms underlying TIMP-1 downregulation in chronic neuroinflammation. We used interleukin (IL)-1, as a model pro-inflammatory stimulus and measured TIMP-1 binding to extracellular matrix, cell death, receptor downregulation, TIMP-1 mRNA stability and transcriptional regulation in activated astrocytes. TIMP-1 remained localized to the cell body or was secreted into the cell supernatant. DNA fragmentation ELISA and MTT assay showed that prolonged IL-1, activation of astrocytes induced significant astrocyte death. In acute and chronic IL-1,-activated astrocytes, IL-1 receptor levels were not significantly different. TIMP-1 mRNA stability was measured in astrocytes and U87 astroglioma cells by real-time PCR, and TIMP-1 promoter activation was studied using TIMP-1-luciferase reporter constructs in transfected astrocytes. Our results indicated that TIMP-1 expression is regulated through multiple mechanisms. Transcriptional control and loss of mRNA stabilization are, however, the most likely primary contributors to chronic downregulation of TIMP-1. These data are important for unraveling the mechanisms underlying astrocyte responses during chronic neuroinflammation and have broader implications in other inflammatory diseases that involve MMP/TIMP imbalance. © 2006 Wiley-Liss, Inc. [source] Ascaris lumbricoides infection is associated with protection from cerebral malariaPARASITE IMMUNOLOGY, Issue 3 2000Mathieu Nacher Following reports of increased IgE in severe malaria and hypothesizing that helminth coinfections could modify its outcome, we conducted a retrospective case,control study to establish whether helminths affect the evolution of Plasmodium falciparum malaria. Some 182 severe cases, 315 mild controls and 40 controls with circulating schizonts were examined for intestinal helminths. Comparing cerebral malaria with mild controls, Ascaris lumbricoides was associated with a protective adjusted odds ratio (OR) of 0.58 (0.32,1.03) P = 0.06, for coinfection with Ascaris and Necator americanus, OR = 0.39 (0.17,0.88) P = 0.02. Protection followed a dose,effect trend (P = 0.008). When comparing cerebral malaria cases and controls with circulating schizonts the OR was 0.25 (0.009,0.67) P = 0.006. We hypothesized that Ascaris infected patients may have had decreased cyto-adherence, possibly through endothelial cell receptor downregulation and/or decreased splenic clearance leading to the absence of selection of virulent P. falciparum strains. IgE-anti-IgE immune complexes resulting from helminth preinfection may have an important role in influencing clinical presentation of severe malaria, and in establishing malaria tolerance, through the CD23/NO pathway. [source] REVIEW ARTICLE: B7 Family Molecules as Regulators of the Maternal Immune System in PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Margaret G. Petroff Citation Petroff MG, Perchellet A. B7 family molecules as regulators of the maternal immune system in pregnancy. Am J Reprod Immunol 2010 Placental and fetal growth and development are associated with chronic exposure of the maternal immune system to fetally derived, paternally inherited antigens. Because maternal lymphocytes are aware of fetal antigens, active tolerance mechanisms are required to ensure unperturbed progression of pregnancy and delivery of a healthy newborn. These mechanisms of tolerance may include deletion, receptor downregulation, and anergy of fetal antigen-specific cells in lymphoid tissues, as well as regulation at the maternal,fetal interface by a variety of locally expressed immunoregulatory molecules. The B7 family of costimulatory molecules comprises one group of immunoregulatory molecules present in the decidua and placenta. B7 family members mediate both inhibitory and stimulatory effects on T-cell activation and effector functions and may play a critical role in maintaining tolerance to the fetus. Here, we review the known functions of the B7 family proteins in pregnancy. [source] Serotonin decreases HIV-1 replication in primary cultures of human macrophages through 5-HT1A receptorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2008B Manéglier Background and purpose: 5-HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5-HT-releasing cell types, mostly platelets. In this study, we investigated the effects of 5-HT on HIV-1-infected macrophages in vitro. Experimental approach: Human macrophages cultured in serum-free medium were treated over 7 days with 5-HT at three concentrations (0.01, 1 and 100 ,M) with or without agonists and antagonists of 5-HT1A and 5-HT2 receptors. After 7 days of treatment, macrophages were infected with HIV-1/Ba-L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV-1/Ba-L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein-1, (MIP-1,), was quantified by ELISA in cell culture supernatants and MIP-1, mRNA expression was assessed by reverse transcriptase-PCR. Key results:In vitro, 5-HT downregulated the membranous expression of CCR5 and led to a decrease of HIV-1 infection, probably through its action on 5-HT1A receptors. 5-HT (100 ,M) was also able to induce overexpression of MIP-1, mRNA leading to an increase of MIP-1, secretion by human macrophages. Conclusions and implications: The effects of 5-HT on HIV infection could be a consequence of the increase in MIP-1, concentrations and/or CCR5 receptor downregulation. These results suggest that 5-HT can inhibit the replication of HIV-1 in primary culture of human macrophages through its action on 5-HT1A receptors. [source] | ||||||||||