Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0012739 (
disseminated intravascular coagulation
)
8,673
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Coagulation proteases may act as cell signaling molecules via protease-activated receptor (PAR) cleavage, subsequently affecting cellular and inflammatory responses. Activation of PARs in the setting of systemic inflammation and
disseminated intravascular coagulation
(
DIC
) might thus exacerbate the inflammatory response contributing to tissue and organ damage. To investigate the role of
PAR-4
in these processes, we subjected mice to a model of systemic inflammation and
DIC
(Shwartzman reaction) in the absence or presence of a cell-penetrating pepducin antagonist of
PAR-4
(P4pal-10). P4pal-10 dose-dependently diminished the severity of endotoxemia and preserved liver, kidney, as well as lung function. Moreover, systemic inflammation and local (neutrophilic) inflammatory responses were attenuated. In vitro migration assays and P4pal-10 treatment in neutropenic mice suggest an essential role for neutrophils in
PAR-4
-mediated pathology. P4pal-10 treatment of thrombocytopenic mice excluded the involvement of platelets in this phenomenon. These results uncover an important role for
PAR-4
in the Shwartzman reaction and suggest that inhibition of
PAR-4
signaling in neutrophils could be protective in systemic inflammation and
DIC
.
...
PMID:Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation. 1764 Dec 6
