title: COX-2 and PGE2 signaling is essential for the regulation of IDO expression by curcumin in murine bone marrow-derived dendritic cells.
abstract: Indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyzes the initial, rate-limiting step in tryptophan degradation, is expressed in dendritic cells (DCs) which are stimulated by lipopolysaccharide (LPS) or interferons. In this study we show that curcumin inhibits IDO expression in vitro and in vivo in DCs, leading to the suppression of LPS-induced DC maturation. The effect of curcumin relative to LPS is not limited to the above, as it also enhances LPS-induced expression of cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2). Additionally, PGE2 diminished the LPS-induced IDO expression in DCs, thereby contributing to the inhibition of expression of the surface molecules (CD80, CD86 and MHC class I) and the production of the proinflammatory cytokines (IL-12 p70 and TNF-alpha) by LPS stimulation. Under our experimental conditions, curcumin plays an immunomodulatory role by downregulating IDO expression via a COX-2/PGE2-dependant pathway, thus impacting DC maturation in vitro and in vivo.
authors.affiliation: Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation & Regulation, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770, South Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Jeong
authors.forename: Sung Hak
authors.initials: SH
authors.lastname: Chun
authors.forename: Oksoon Hong
authors.initials: OH
authors.lastname: Choi
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.forename: Han Wool
authors.initials: HW
authors.lastname: Kim
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism*; D056747:Immunomodulation; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003474:Curcumin; D015232:Dinoprostone