TY - JOUR
T1 - The induction of prostaglandin E synthase and upregulation of cyclooxygenase-2 by 9-cis retinoic acid
AU - Tsukamoto, Hiroki
AU - Hishinuma, Takanori
AU - Tayama, Risa
AU - Narahara, Kaori
AU - Suzuki, Naoto
AU - Tomioka, Yoshihisa
AU - Goto, Junichi
PY - 2004/10/1
Y1 - 2004/10/1
N2 - 9-cis Retinoic acid (9cRA) is a promising lead compound to design the retinoid X receptor (RXR) ligands with the ability to simultaneously activate RXR heterodimers with the selectivity to their nuclear receptor partners. In this study, we investigated the effects of 9cRA on the prostaglandin E 2 (PGE 2) and thromboxane A 2 (TXA 2) production. 9cRA increased the PGE 2 and TXA 2 productions in the presence of lipopolysaccharide (LPS). All-trans retinoic acid, the retinoic acid receptor ligand, also increased their production. We revealed that cyclooxygenase (COX)-2 was clearly induced by 9cRA in the presence of LPS. The induction was not suppressed by indomethacin, which completely inhibited the increase in the LPS-stimulated prostanoid production by 9cRA. The expression levels of the toll-like receptor 4 and CD14, which were components of the LPS receptor complex, were increased by 9cRA in the presence and absence of LPS. PGE synthase was also clearly increased by 9cRA in the presence and absence of LPS. In this study, we noted that 9cRA increased the production of PGE 2 and TXA 2 by the induction of COX-2 and PGE synthase in the presence of LPS. The induction of the LPS receptor complex by 9cRA is able to upregulate the induction of COX-2 by LPS.
AB - 9-cis Retinoic acid (9cRA) is a promising lead compound to design the retinoid X receptor (RXR) ligands with the ability to simultaneously activate RXR heterodimers with the selectivity to their nuclear receptor partners. In this study, we investigated the effects of 9cRA on the prostaglandin E 2 (PGE 2) and thromboxane A 2 (TXA 2) production. 9cRA increased the PGE 2 and TXA 2 productions in the presence of lipopolysaccharide (LPS). All-trans retinoic acid, the retinoic acid receptor ligand, also increased their production. We revealed that cyclooxygenase (COX)-2 was clearly induced by 9cRA in the presence of LPS. The induction was not suppressed by indomethacin, which completely inhibited the increase in the LPS-stimulated prostanoid production by 9cRA. The expression levels of the toll-like receptor 4 and CD14, which were components of the LPS receptor complex, were increased by 9cRA in the presence and absence of LPS. PGE synthase was also clearly increased by 9cRA in the presence and absence of LPS. In this study, we noted that 9cRA increased the production of PGE 2 and TXA 2 by the induction of COX-2 and PGE synthase in the presence of LPS. The induction of the LPS receptor complex by 9cRA is able to upregulate the induction of COX-2 by LPS.
KW - 9-cis Retinoic acid
KW - Cyclooxygenase-2
KW - Prostaglandin E synthase
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U2 - 10.1016/j.prostaglandins.2004.07.001
DO - 10.1016/j.prostaglandins.2004.07.001
M3 - Article
C2 - 15560116
AN - SCOPUS:5444235597
SN - 0090-6980
VL - 74
SP - 61
EP - 74
JO - Journal of Lipid Mediators
JF - Journal of Lipid Mediators
IS - 1-4
ER -