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Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of(More)
The mitogen-activated protein kinase (MAPK) pathway plays a critical role in Toll-like receptor (TLR) signaling. MAPK phosphatase-1 (MKP-1) inhibits the MAPK pathway and decreases TLR signaling, but the regulation of MKP-1 is not completely understood. We now show that MKP-1 is acetylated, and that acetylation regulates its ability to interact with its(More)
Cerebellar ataxias, which comprise a wide spectrum of progressive disorders, are incurable at present. It has been reported that human umbilical mesenchymal stem cell (HU-MSC) transplantation has a protective effect on neurodegenerative diseases. In this study, we investigated the effect of HU-MSCs on ataxic mice induced by cytosine beta-D-arabinofuranoside(More)
Intracerebral hemorrhage (ICH) is a devastating form of stroke. Misoprostol, a synthetic prostaglandin E1 (PGE1) analog and PGE2 receptor agonist, has shown protection against cerebral ischemia. In this study, we tested the efficacy of misoprostol in the 12-month-old mice subjected to 1 of 2 complementary ICH models, the collagenase model (primary study)(More)
Cerebral deposition of amyloid-beta peptide (Abeta) is a critical feature of Alzheimer's disease (AD). Either aluminium trichloride (Al) or D-galactose (D-gal) induces Abeta overproduction in rat or mouse brain and has been used to produce models of aging and AD. Here it is shown that mice treated with Al plus D-gal represent a good model of AD with altered(More)
Ischemic stroke can induce immediate activation and later inhibition of the peripheral immune system which may contribute to a worse outcome. Cocaine-and amphetamine-regulated transcript (CART) peptides have been reported to have neuroprotective and immunomodulatory effects in various cell and animal experimental models, respectively. In this study, CART's(More)
BACKGROUND Inducible nitric oxide synthase (iNOS, or NOS2) reduces the severity of accelerated graft arteriosclerosis (AGA) in transplanted organs, although the precise mechanism is unclear. METHODS AND RESULTS We transplanted wild-type murine hearts into either wild-type or NOS2-null recipient mice; we then measured cardiac allograft survival and(More)
Inflammation is an important contributing mechanism in ischemic brain injury. The current study elucidates a previously unexplored role of Fas ligand (FasL) in post-stroke inflammatory responses that is independent of its well-known effect in triggering apoptosis. Focal cerebral ischemia was induced for 2 h by right middle cerebral artery occlusion (MCAO)(More)
Carbon monoxide (CO) released from CORM-2 has anti-inflammatory function, but the critical molecule mediating the inflammation inhibition has not been elucidated. Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating host defense against oxidative stress and inflammation-related disorders. In this study we use Nrf2(More)
Nitric oxide (NO) is an antiviral effector of the innate immune system, but few of the viral targets of NO have been identified. We now show that NO inhibits adenovirus replication by targeting the adenovirus proteinase (AVP). NO generated from diethylamine NONOate (DEA-NONOate) or spermine NONOate (Sp-NONOate) inhibited the AVP. Inhibition was reversible(More)