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.

Abstract. Proteinase-activated receptor-2 (PAR2) triggers upregulation of cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) formation in human alveolar epithelial A549 cells. This COX-2 upregulation appears to involve the Src / epidermal growth factor (EGF) receptor / p38 MAP kinase (p38MAPK) pathway and also the cAMP-response element-binding protein (CREB) pathway. Here, we investigated the roles of nuclear factor-κB (NF-κB)-related signals in the PAR2-triggered PGE 2 release / COX-2 upregulation in A549 cells. The PAR2-triggered PGE 2 release was clearly blocked by an inhibitor of the NF-κB pathway. Stimulation of PAR2 actually caused phosphorylation of inhibitor-κB, an indicator of NF-κB activation, an effect being blocked by inhibitors of MEK, phosphatidylinositol 3-kinase (PI3-kinase), and Akt, but little or not by inhibitors of p38MAPK and JNK. Stimulation of PAR2 also caused phosphorylation of Akt, an effect suppressed by inhibitors of PI3-kinase and MEK. Nonetheless, the PAR2-triggered upregulation of COX-2 was resistant to inhibitors of NF-κB, PI3-kinase, and Akt, but was attenuated by inhibitors of MEK and JNK. Stimulation of PAR2 induced phosphorylation of CREB, an effect abolished by an inhibitor of MEK but not inhibitors of p38MAPK and EGF receptor. These findings demonstrate that the MEK / ERK / PI3-kinase / Akt / NF-κB pathway is involved in PAR2-triggered PGE 2 formation, but not upregulation of COX-2 that is dependent on activation of ERK /CREB and JNK in addition to p38MAPK.

Due to the Corona situation, teleworking practices and relocations have increased, as people realize that they can do their jobs from any location. People have been relocating and buying land in remote and rural regions, away from the risks associated with the ongoing pandemic and inner-city living. The author of this paper has made several promotion films, documenting the initiatives of local people in the mountainous rural Ashimi district of Fukui Prefecture, and has been researching to verify and describe the results of these video expressions by comparing them to similar projects from different regions both in Japan and around the world. This paper researched the works of Japan World’s Tourism Film Festival, which the author was also involved in managing, and used text mining to find keywords required to improve and objectively verify results.