title: Enhanced IL-12p40 production in LPS-stimulated macrophages by inhibiting JNK activation by artemisinin.
abstract: Artemisinin can be isolated from Artemisia annua L. In addition to its well-known anti-malarial activity, artemisinin has antitumor and anti-microbial effects. In this study, we investigated the effect of artemisinin on the production of IL-12p40, which is important in the generation of T helper 1 responses. Artemisinin significantly induced IL-12p40 production in LPS-stimulated RAW264.7 macrophage cells. To elucidate the signaling molecules regulated by artemisinin in induced IL-12p40 production, the DNA-binding activity of several transcription factors and activation of mitogen-activated protein kinase (MAPK)s were investigated. The band intensities of NF-κB, AP-1, and SP1, and the activation of p38 MAPK and ERK were not changed by artemisinin. However, the induced phosphorylation of JNK was significantly decreased by artemisinin, and inhibition of the JNK signaling pathway further increased IL-12p40 production in LPS-stimulated RAW264.7 macrophage cells. Taken together, these data suggest that artemisinin induces the production of IL-12p40 in LPS-stimulated macrophage cells by inhibiting JNK activity.
authors.affiliation: College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Young-Chang
authors.initials: YC
authors.lastname: Cho
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Mina
authors.initials: M
authors.lastname: Lee
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Oak
authors.forename: Ik-Soo
authors.initials: IS
authors.lastname: Lee
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
mesh_terms: D000818:Animals; D031172:Artemisia annua / Q000737:chemistry*; D037621:Artemisinins / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018417:Th1 Cells / Q000378:metabolism
chemical_list: D037621:Artemisinins; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; C031327:artemisinin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases