mmi-0100 and Disease-Models--Animal

Topics: Administration, Intranasal; Alzheimer Disease; Amyloid beta-Peptides; Animals; Astrocytes; Autoantigens; Cells, Cultured; Cytokines; Disease Models, Animal; Hippocampus; Humans; Inflammation Mediators; Male; MAP Kinase Kinase 2; Memory Disorders; Mice; Mice, Inbred Strains; Neurogenic Inflammation; Peptide Fragments; Peptides; Signal Transduction

ICAM-1 plays a critical role in the development of acute respiratory distress syndrome (ARDS). MK2 regulates the expression of ICAM-1 in human pulmonary microvascular endothelial cells. To explore whether the inhibition of MK2 activation has the same effect in experimental animals, MMI-0100, a peptide-mediated inhibitor of MK2, was used to verify whether MMI-0100 can ameliorate lung inflammation in a mouse model of ARDS by reducing endothelial expression of ICAM-1.. In this study, C57BL/6 mice were randomly divided into three groups: a control group, an lipopolysaccharides (LPS) group, and an LPS plus MMI-0100 group. Mice were killed 24 hours after the administration of LPS and MMI-0100. The mouse lung tissue histopathology, wet/dry weight ratio (W/D), and the neutrophil count were used to measure the severity of lung inflammation in mice. The pulmonary microvascular endothelial cells (PMVECs) of the mice were isolated. The mRNA expression of ICAM-1 in mouse PMVECs was determined using RT-PCR, and the protein expression of MK2 and ICAM-1 in mouse PMVECs was analyzed using Western blotting and immunohistochemistry.. We found that the level of phosphorylated MK2 in the LPS plus MMI-0100 group was reduced. Compared with the LPS group, the LPS plus MMI-0100 group of mice showed less severe inflammation, including a lower W/D and neutrophil count. The mRNA and protein expression of ICAM-1 in the LPS group was significantly higher than in the control group in mouse PMVECs, and the ICAM-1 level was reduced after the administration of MMI-0100.. These data indicate that MMI-0100 ameliorates lung inflammation in a mouse model of ARDS by reducing endothelial expression of ICAM-1.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Down-Regulation; Endothelial Cells; Intercellular Adhesion Molecule-1; Intracellular Signaling Peptides and Proteins; Lipopolysaccharides; Lung; Male; Mice, Inbred C57BL; Peptides; Phosphorylation; Pneumonia; Protein Serine-Threonine Kinases; Respiratory Distress Syndrome

Cardiac stress can trigger production of a 40-kDa peptide fragment derived from the amino terminus of the cardiac myosin-binding protein C. Cardiac stress, as well as cMyBP-C mutations, can trigger production of 1 such truncated protein fragment, a 40-kDa peptide fragment derived from the amino terminus of cMyBP-C. Genetic expression of this 40-kDa fragment in mouse cardiomyocytes (cMyBP-C. Nontransgenic and cMyBP-C. Pharmaceutical inhibition of mitogen-activated protein kinase--activated protein kinase-2 signaling via MMI-0100 treatment is beneficial in the context of fibrotic cMyBPC

Topics: Actins; Animals; Cardiomyopathies; Carrier Proteins; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Fibroblasts; Fibrosis; Hypertrophy, Left Ventricular; Intracellular Signaling Peptides and Proteins; Mice, Inbred C57BL; Mice, Transgenic; Myocytes, Cardiac; Peptides; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Up-Regulation; Ventricular Remodeling