Curcumin Inhibits the proteinase-activated receptor-2-triggered prostaglandin E2 production by suppressing cyclooxygenase-2 upregulation and Akt-dependent activation of nuclear factor-κB in human lung epithelial cells.
We performed this study to determine if curcumin affects pro-inflammatory responses to activation of proteinase-activated receptor-2 (PAR2) in human pulmonary adenocarcinoma A549 cells. Curcumin completely inhibited the PAR2-triggered prostaglandin E(2) (PGE(2)) production, but notably not interleukin-8 release. Cyclooxygenase-2 (COX-2) upregulation, but not its upstream activation of mitogen-activated protein kinases, caused by PAR2 stimulation was partially inhibited by curcumin. Curcumin inhibited the PAR2-triggered phosphorylation of I-κB, an indicator for nuclear factor-κB (NF-κB) activation, and also its upstream signal Akt, which is known to contribute to PAR2-triggered PGE(2) formation, but not COX-2 upregulation. Collectively, curcumin inhibits the PAR2-triggered PGE(2) production by suppressing COX-2 upregulation and Akt/NF-κB signals in A549 cells.
Moriyuki
Kazumi
K
Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Japan.
Sekiguchi
Fumiko
F
Matsubara
Kaori
K
Nishikawa
Hiroyuki
H
Kawabata
Atsufumi
A
D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D016328:NF-kappa B; D044464:Receptor, PAR-2; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin; D015232:Dinoprostone