Abstract
We investigated the signaling pathway that leads to the expression of heme oxygenase-1 (HO-1) in murine macrophages in response to 15-deoxy-delta 12,14-prostaglandin J2 (15dPGJ2). 15dPGJ2 caused dose- and time-dependent activation of Rac1, followed by a transient increase in reactive oxygen species (ROS) via NADPH oxidase, which leads to downstream activation of p38 kinase. Inhibition of 15dPGJ2-dependent HO-1 expression significantly attenuated suppression by 15dPGJ2 of LPS-induced iNOS expression and subsequent production of nitric oxide (NO). Our findings strongly suggest that 15dPGJ2 exerts its anti-inflammatory activity through the Rac1-NADPH oxidase-ROS-p38 signaling to the up-regulation of HO-1 in an in vitro inflammation model.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
-
Cell Line
-
Heme Oxygenase-1 / metabolism*
-
Inflammation / enzymology
-
Inflammation / immunology*
-
Macrophages / drug effects*
-
Macrophages / enzymology
-
Macrophages / immunology
-
Mice
-
NADPH Oxidases / metabolism
-
Neuropeptides / metabolism
-
Prostaglandin D2 / analogs & derivatives*
-
Prostaglandin D2 / pharmacology
-
Reactive Oxygen Species / metabolism
-
Signal Transduction
-
Up-Regulation*
-
p38 Mitogen-Activated Protein Kinases / metabolism
-
rac GTP-Binding Proteins / metabolism
-
rac1 GTP-Binding Protein
Substances
-
15-deoxy-delta(12,14)-prostaglandin J2
-
Anti-Inflammatory Agents, Non-Steroidal
-
Neuropeptides
-
Rac1 protein, mouse
-
Reactive Oxygen Species
-
Heme Oxygenase-1
-
NADPH Oxidases
-
p38 Mitogen-Activated Protein Kinases
-
rac GTP-Binding Proteins
-
rac1 GTP-Binding Protein
-
Prostaglandin D2