COX-2 and PGE2 signaling is essential for the regulation of IDO expression by curcumin in murine bone marrow-derived dendritic cells.
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.
Jung
In Duk
ID
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.
Jeong
Young-Il
YI
Lee
Chang-Min
CM
Noh
Kyung Tae
KT
Jeong
Soo Kyung
SK
Chun
Sung Hak
SH
Choi
Oksoon Hong
OH
Park
Won Sun
WS
Han
Jin
J
Shin
Yong Kyoo
YK
Kim
Han Wool
HW
Yun
Cheol-Heui
CH
Park
Yeong-Min
YM
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
D000943:Antigens, Differentiation; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003474:Curcumin; D015232:Dinoprostone