Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benznidazole (BZL) is a nitroheterocyclic drug employed in the chemotherapy of Chagas' disease, a protozoan disease caused by Trypanosoma cruzi. Because this parasite mostly replicates in macrophages, we investigated whether BZL was likely to modify the synthesis of macrophage mediators such as nitrite, tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-10. Control and stimulated murine macrophages (lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma)) were treated with BZL and measurements were carried out in culture supernatants collected 24 h later. Synthesis of nitrite, IL-6 and IL-10 was maximal upon combined stimulation with LPS + IFN-gamma, whereas lower amounts of the three mediators were detected when both stimuli were given alone. BZL treatment significantly reduced nitrite, IL-6 and IL-10 production, to undetectable levels in some cases, particularly IL-6 and IL-10. LPS was the most potent stimulus of IL-1beta and TNF-alpha production, followed by LPS + IFN-gamma and IFN-gamma in decreasing order. BZL partly inhibited TNF-alpha synthesis, but this effect was smaller than that observed for nitrite, IL-6 and IL-10. LPS-induced production of IL-1beta was also affected by BZL. Semiquantification of gene expression for inducible nitric oxide synthase (iNOS) showed that BZL completely inhibited iNOS gene induction by IFN-gamma, and resulted in respective inhibitions of 30% and 50% with LPS- and LPS + IFN-gamma-stimulated cells. BZL was not cytotoxic on macrophage cultures, as shown by the lactate dehydrogenase activity. Besides its trypanocidal activity, BZL may also alter the balance between pro- and anti-inflammatory mediators with important consequences for the course of T. cruzi infection.
 ...
PMID:Benznidazole, a drug employed in the treatment of Chagas' disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages. 1054 Jan 90

Trypanosoma cruzi, the etiological agent of Chagas' disease, may persist for many years in its mammalian host. This suggests escape from the immune response and particularly a suboptimal CD8(+) T cell response, since these cells are involved in infection control. In this report, we show that T. cruzi inhibits the lipopolysaccharide (LPS)-induced up-regulation of MHC class I molecules at the surface of human dendritic cells (DC). To further investigate the functional consequences of this inhibition, a trypomastigote surface antigen-derived peptide (TSA-1(514-522) peptide) was selected for its stable binding to HLA-A*0201 molecules and used to generate a primary T. cruzi-specific human CD8(+) T cell line in vitro. We observed that DC infected with T. cruzi or treated with T. cruzi-conditioned medium (TCM) had a weaker capacity to present this peptide to the specific CD8(+) T cell line as shown in an IFN-gamma ELISPOT assay. Interestingly, T. cruzi or TCM also reduced the antigen presentation capacity of DC to CD8(+) T cell lines specific for the influenza virus M(58-66) or HIV RT(476-484) epitopes. This dysfunction appears to be linked essentially to reduced MHC class I molecule expression since the stimulation of the RT(476-484) peptide-specific CD8(+) T cell line was shown to depend mainly on the MHC class I-TCR interaction and not on the co-stimulatory signals which, however, were also inhibited by T. cruzi. This impairment of DC function may represent a novel mechanism reducing in vivo the host's ability to combat efficiently T. cruzi infection.
 ...
PMID:Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes. 1235 79

Trypanosoma cruzi, the protozoan that causes Chagas' heart disease, invades endothelial cells in vitro by activating the B2 kinin receptor (B2R). Here, we demonstrate that mice infected with trypomastigotes develop potent edema after treatment with the angiotensin-converting enzyme (ACE) (or kininase II) inhibitor captopril. Experiments performed with specific kinin receptor (B2R/B1R) antagonists and knockout mice revealed that the early-phase (3-h) edema is mediated by the constitutive B2R, whereas the late-phase (24-h) response depends on stimulation of the up-regulated B1R. Given previous evidence that parasite invasion of cells expressing B2R is potentiated by captopril, we investigated the prerequisites for in vitro infection of Chinese hamster ovary cells overexpressing either B1R or B2R, human umbilical vein endothelial cells activated by lipopolysaccharide, and neonatal rat cardiomyocytes. Our results indicate that captopril potentiates parasite invasion regardless of the kinin (B2/B1) activation pathways, whereas DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MGTA), an inhibitor of kininase I (carboxypeptidase M/N), selectively decreases parasite infectivity for B1R-expressing cells. These data suggest that formation of the B1R agonist, i.e., [des-Arg] kinins, critically depends on the processing action of kininase I, here proposed as a potential pathogenesis cofactor. Collectively, our data suggest that fluctuations in the levels of kininases may modulate parasite infectivity and pathological outcome in Chagas' disease.
 ...
PMID:Trypanosoma cruzi induces edematogenic responses in mice and invades cardiomyocytes and endothelial cells in vitro by activating distinct kinin receptor (B1/B2) subtypes. 1242 28

Trypanosoma cruzi, the etiologic agent of Chagas disease, induces infection that affects most immunocompetent cells. However, its effect on dendritic cells (DC) is still unknown in vivo. In this report, we show, by immunohistochemical staining, that T. cruzi infection triggers a huge increase in the number of CD11c(+) DC in the spleen of infected mice at Days 14 and 21 post-inoculation (pi). In mice reaching the chronic phase (starting on Day 35 pi), the number of splenic DC (sDC) returned progressively to normal (ending on Day 98 pi). In the spleens of noninfected mice, most of the CD8alpha(+)CD11c(+) and CD8alpha(-)CD11c(+) DC were found in the red pulp and the marginal and T-cell zones. However, starting on Day 14 pi, a progressive decline of CD8alpha(+)CD11c(+) was observed. In addition, sDC expressed low levels of the costimulatory molecule B7.2 at Days 14 and 21 pi, suggesting that they remained immature in the course of the infection. As expected, in lipopolysaccharide-treated and noninfected mice, the expression of B7.2 molecules was sharply up-regulated on sDC that migrated toward the T-cell zone. In contrast, upon lipopolysaccharide stimulation, sDC from T. cruzi-infected mice did not migrate toward the T-cell zone nor did they undergo maturation. Finally, white pulp was severely depleted in both CD4(+) and CD8(+) T cells at the peak of infection. Taken together, these results indicate that profound alterations of migration and maturation of sDC and depletion/redistribution of T cells occur during the acute phase of T. cruzi infection and could be part of another strategy to escape immune surveillance and to persist in the host.
 ...
PMID:Alteration of migration and maturation of dendritic cells and T-cell depletion in the course of experimental Trypanosoma cruzi infection. 1367 45

Nitric oxide (NO) is a key immune effector and signaling molecule in many organisms. However, the contribution NO makes towards insect immunity has received little attention, particularly in non-dipteran species. In this study, tissue- and time-specific alterations in NO synthase (NOS) gene expression and NO production were documented in the hemipteran vector of Chagas' disease, Rhodnius prolixus, following in vivo immune challenge by Trypanosoma cruzi, T. rangeli and crude bacterial lipopolysaccharide (LPS). The most pronounced reactions to crude LPS occurred in major immune tissues (fat body and blood cells), while tissues of the digestive tract were most responsive to infections by T. cruzi and T. rangeli. The data suggest the NO-mediated immune responses of R. prolixus are pathogen-specific and independently modified both at the transcriptional and enzyme levels.
 ...
PMID:Differential modulation of Rhodnius prolixus nitric oxide activities following challenge with Trypanosoma rangeli, T. cruzi and bacterial cell wall components. 1745 39

The use of blood donor history and state-of-the-art FDA-licensed serological and nucleic acid testing (NAT) assays have greatly reduced the "infectious window" for several transfusion-transmitted pathogens. Currently transmission of human immunodeficiency virus (HIV), Human T-cell Lymphotropic Virus (HTLV), hepatitis viruses and West Nile Virus are rare events. The seroprevalence of cytomegalovirus in the donor population is high and cytomegalovirus infection can cause significant complications for immunocompromised recipients of blood transfusion. Careful use of CMV seronegative blood resources and leukoreduction of blood products are able to prevent most CMV infections in these patients. Currently, bacterial contamination of platelet concentrates is the greatest remaining infectious disease risk in blood transfusion. Specialized donor collection procedures reduce the risk of bacterial contamination of blood products; blood culture and surrogate testing procedures are used to detect potential bacterially contaminated platelet products prior to transfusion. A rapid quantitative immunoassay is now available to test for the presence of lipotechoic acid and lipopolysaccharide bacterial products prior to platelet transfusion. Attention has now turned to emerging infectious diseases including variant Creutzfeldt-Jakob disease, dengue, babesiosis, Chagas' disease and malaria. Challenges are presented to identify and prevent transmission of these agents. Several methods are being used or in development to reduce infectivity of blood products, including solvent-detergent processing of plasma and nucleic acid cross-linking via photochemical reactions with methylene blue, riboflavin, psoralen and alkylating agents. Several opportunities exist to further improve blood safety through advances in infectious disease screening and pathogen inactivation methods.
 ...
PMID:Approaches to minimize infection risk in blood banking and transfusion practice. 2130 41

Inflammation is powerful response to destroy invading organisms, and an exaggerated response can lead to death of the host. Macrophages secrete mediators that activated circulating neutrophils leading to its migration into infectious site. Recently, it has been shown that lymphocytes have an action modulating the early phase of inflammatory response. In this article, we analyze the role of B1 in the inflammatory response of different origins and finally focus attention on sepsis. B lymphocyte deficiency has been linked to acute infection presumably owing to the lack of an adaptive immune response to effectively clear pathogens. Individuals with X-linked agammaglobulinemia (XLA) present B1 lymphocyte deficiency caused by mutations in the Bruton tyrosine kinase (Btk). Some data show that B1 cells might contribute to susceptibility in experimental paracoccidioidomycosis. On the other hand, B1 cells are shown to be detrimental in other mouse models of microbial infection, such as experimental Chagas disease, leishmaniasis, and Staphylococcus aureus-induced arthritis. B1 cell plays a protective role in the host of the effects of endotoxemia. In a murine model of endotoxemia by lipopolysaccharide, B1 cell participates in both interleukin 10 and immunoglobulin M secretion with a consequent reduction in mortality.
 ...
PMID:Inflammatory response: role of B1 cells. 2348 95

Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.
...
PMID:Sympathetic glial cells and macrophages develop different responses to Trypanosoma cruzi infection or lipopolysaccharide stimulation. 2507 84


<< Previous 1 2