Macrophage apoptosis is an important component of the innate immune defense machinery (against pathogenic mycobacteria) responsible for limiting bacillary viability. However, little is known about the mechanism of how apoptosis is executed in mycobacteria-infected macrophages. Apoptosis signal-regulating kinase 1 (ASK1) was activated in Mycobacterium avium-treated macrophages and in turn activa...

Vascular remodeling in hypertension is associated with cell growth and increased deposition of extracellular matrix components, particularly collagen. Mechanisms underlying these processes are unclear, but MAP kinases, particularly ERK1/2 and p38 MAP kinase, may be important. We studied the role of ERK1/2 and p38 MAP kinase in vascular smooth muscle cell (VSMC) collagen synthesis and growth med...

The role of stress-activated protein kinases (SAPKs), c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase, in preconditioning (PC) was examined with the use of isolated rat hearts subjected to four cyclic episodes of 5-min ischemia and 10-min reperfusion followed by 30-min ischemia and 2-h reperfusion (I/R). A group of hearts was preperfused with 100 microM curcumin...

No currently available treatments reduce the progression of chronic obstructive pulmonary disease (COPD) or suppress the inflammation in small airways and lung parenchyma. However, several new treatments now in development for COPD are targeted at the inflammation process. Antagonists of mediators, such as leukotriene B4, interleukin-8, and tumour necrosis factor-alpha and inhibitors of oxidati...

Increases in extracellular calcium concentration ([Ca(2+)](o)) stimulate from normal and malignant cells secretion of parathroid hormone-related protein (PTHrP), a major mediator of humoral hypercalcemia of malignancy. Because the calcium-sensing receptor (CaR) is a determinant of calcium-regulated hormone secretion, we examined whether HEK cells stably transfected with human CaR secreted PTHrP...

The aim of this study was to examine the role of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-8 expression in tumour necrosis factor (TNF)-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells. To this end, the phosphorylation and activation of p38 MAP kinase and the effect of SB 203580, a specific inhibitor of p38 MAP kinase activity, on p38 MAP kinase ac...

Mitogen-activated protein (MAP) kinases belong to a highly conserved family of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological functions. The 4 best-characterized MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, have been implicated in different aspects of cardiac regulation, from development to pathological remodeling. Recent advancements in the develo...

Coupling of M(2) and M(3) muscarinic receptors to activation of mitogen-activated protein (MAP) kinases and phosphorylation of caldesmon was studied in canine colonic smooth muscle strips in which M(3) receptors were selectively inactivated by N, N-dimethyl-4-piperidinyl diphenylacetate (4-DAMP) mustard (40 nM). ACh elicited activation of extracellular signal-regulated kinase (ERK) 1, ERK2, and...

Many receptor-linked agents that prime or activate the NADPH oxidase in polymorphonuclear neutrophils (PMNs) elicit changes in cytosolic Ca2+ concentration and activate mitogen-activated protein (MAP) kinases. To investigate the role of Ca2+ in the activation of p38 and p42/44 MAP kinases, we examined the effects of the Ca2+-selective ionophore ionomycin on priming and activation of the PMN oxi...

The function of vascular endothelium as a biomechanical sensor permits alterations in gene expression in the vascular tree in response to wall stress. The present study explored the mechanism by which the arterial endothelium responds to changes in dietary salt. Normotensive rats were fed diets containing varying amounts of NaCl for 4 days. At that time, levels of phosphorylated p38 MAP kinase,...