BACKGROUND/AIMS This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts. METHODS Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovi...

The role of p38 mitogen-activated protein (MAP) kinase, and extracellular-regulated protein kinase -1 and -2 in regulating constitutive apoptosis and interleukin (IL)-5-induced survival of human eosinophils have been investigated. Two populations of donors were identified whose eosinophils, in the absence of exogenous cytokines, underwent apoptosis at different rates. Eosinophils were thus arbi...

To study the mechanisms by which catecholamines regulate hepatocyte proliferation after partial hepatectomy (PHX), hepatocytes were isolated from adult male rats 24 h after sham operation or two-thirds PHX and treated with catecholamines and other agonists. In freshly isolated sham cells, p42 mitogen-activated protein (MAP) kinase activity was stimulated by the alpha1-adrenergic agonist phenyle...

BACKGROUND Vein grafting in coronary artery surgery is complicated by a high restenosis rate resulting from the development of vascular inflammation, intimal hyperplasia, and accelerated atherosclerosis. In contrast, arterial grafts are relatively resistant to these processes. Vascular inflammation is regulated by signaling intermediaries, including p38 mitogen-activated protein (MAP) kinase, t...

parkinson's disease (pd) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring alzheimer's disease (ad). currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of pd. out of several factors contributing to pd prognosis, the role of p38 mapks (mitog...

The serum response element (SRE), which is pivotal for transcriptional up-regulation of the c-fos protooncogene, is constitutively occupied by a protein complex comprising the serum response factor and a ternary complex factor (TCF). Phosphorylation of the TCFs Elk-1 and Sap-1a by the ERK and JNK subclasses of MAP kinases triggers c-fos transcription. We demonstrate here that Elk-1 is barely ac...

It has been shown that p38 mitogen-activated protein (MAP) kinase is absolutely necessary for the cardioprotection of early ischemic preconditioning in the heart. Reorganization of actin cytoskeleton after translocation of HSP27, which is mediated by p38 MAP kinase, was reported to be necessary for the cardioprotective effect of early ischemic preconditioning. Although Rho and Rho kinase are re...

MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 m...

Reduced activity and expression of endothelial NO synthase (eNOS) is observed in cardiomyocytes from pressure-overloaded hearts with heart failure. The present study was aimed to investigate whether reduced eNOS-derived NO production contributes to the hypertrophic growth and phenotype of these cardiomyocytes. Cultured ventricular cardiomyocytes from adult rats were exposed to Nomega-nitro-l-ar...

The clinical course of mycobacterial infections is linked to the capacity of pathogenic strains to modulate the initial antimycobacterial response of the macrophage. To elucidate some of the mechanisms involved, we studied early signal transduction events leading to cytokine formation by human monocyte-derived macrophages (MDM) in response to clinical isolates of Mycobacterium avium. TNF-alpha ...