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)

Murine cytomegalovirus (MCMV) infection of BALB/c mice produces acute and chronic myocarditis similar to clinical disease in humans. In contrast, MCMV-infected C57BL/6 mice develop only mild acute myocarditis. We have investigated the effect of administration of the immunomodulator lipopolysaccharide (LPS) on the development of postviral myocarditis in mice. LPS exacerbated heart inflammation in both strains of MCMV-infected mice, with normally resistant C57BL/6 mice developing chronic myocarditis. Autoantibodies to cardiac myosin were enhanced with LPS treatment in both MCMV-infected mouse strains. LPS treatment also increased the production of TNF in the sera without affecting virus titers in the spleen, liver, or salivary glands, a target organ most affected during persistent virus infection. In LPS/MCMV-infected BALB/c mice, TNF, IL-6, and IL-10 levels were detected in cultures of heart infiltrating cells but not in splenocytes. Importantly, administration of the bioactive synthetic TNF peptide (amino acids 114-130) increased myocarditis in C57BL/6 mice, similar to that seen with LPS treatment. TNF peptide/MCMV-infected BALB/c and C57BL/6 mice showed distinct differences in the expression pattern of IFN-gamma, IL-10, and TNF. These data show that the disease may be partly regulated by TNF among other select cytokines and autoantibodies to cardiac myosin. The immunopathological nature of MCMV-induced myocarditis is thus highlighted.
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PMID:Immunomodulation of murine cytomegalovirus-induced myocarditis in mice treated with lipopolysaccharide and tumor necrosis factor. 1174 56

This chapter describes four murine models of autoimmune diseases: two related to autoimmune myocarditis and two related to autoimmune thyroiditis. The first model, Coxsackie virus B3 (CB3)-induced myocarditis, results in the development of acute myocarditis in susceptible as well as resistant mouse strains, whereas chronic myocarditis develops only in genetically susceptible mice. CB3-induced myocarditis closely resembles the course of human myocarditis, which is believed to be initiated by viral infection. Mouse cardiac myosin heavy chain has been identified as the major antigen associated with the late chronic phase of viral myocarditis. The second model is cardiac myosin-induced experimental autoimmune myocarditis (EAM) and, in a modification, cardiac alpha-myosin heavy chain peptide-induced myocarditis. In the EAM model, cardiac myosin or the relevant peptide in Freund's complete adjuvant (FCA) is injected subcutaneously into mice. The immune response, the histological changes, and the genetic susceptibility seen in EAM are similar to those of CB3-induced myocarditis. The third model is experimental autoimmune thyroiditis (EAT). EAT can be induced in genetically susceptible strains of mice by immunization with mouse thyroglobulin in FCA or lipopolysaccharide. Mice susceptible to EAT have the H-2A(k), H-2A(s), or H-2A(q) alleles. We describe here a standard technique for the induction of EAT; it was developed in our laboratory and is widely used as a model for studying Hashimoto's thyroiditis. The fourth model presented in this chapter is that of spontaneous autoimmune thyroiditis in NOD.H2h4 mice. These mice express the H-2A(k) allele on an NOD genetic background and develop spontaneous thyroiditis, which is exacerbated with dietary iodine.
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PMID:Animal models for autoimmune myocarditis and autoimmune thyroiditis. 1528 86

This study aims to investigate the effects of microRNA (miR)-16/dedicator of cytokinesis 2 (DOCK2) on myocarditis. The differences in the expression of genes in acute myocarditis were filtered out across Gene Expression Omnibus (GEO) database. Myocarditis cell model was established by lipopolysaccharide (LPS) stimulation in cardiomyocytes. The association between miR-16 and DOCK2 was predicted by bioinformatics software and confirmed by dual-luciferase assay. Polymerase chain reaction and western blot analysis were employed to assess the expression levels of miR-16 and DOCK2 under different conditions. Cells viability, apoptosis, and inflammatory reaction were evaluated by Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. miR-16, as an upstream regulator of DOCK2, exhibited lower expression in LPS-induced myocarditis model. More importantly, we revealed that a marked augmentation of miR-16 promoted the growth of LPS-stimulated cardiomyocytes, and attenuated cell apoptosis and inflammatory response. However, an increasing expression of DOCK2 inhibited the remission of LPS-induced myocardial injury caused by miR-16 mimic. Herein, our results highlighted that upregulation of miR-16 resulted in the protective effects on LPS-induced myocardial injury by reducing DOCK2 expression, affording a pair of novel target molecules for ameliorating the symptoms of myocarditis.
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PMID:miR-16 exhibits protective function in LPS-treated cardiomyocytes by targeting DOCK2 to repress cell apoptosis and exert anti-inflammatory effect. 3236 53