TY - JOUR
T1 - Retinoic acid and lipopolysaccharide act synergistically to increase prostanoid concentrations in rats in vivo
AU - Devaux, Yvan
AU - Seguin, Carole
AU - Grosjean, Sandrine
AU - De Talancé, Nicole
AU - Schwartz, Maryline
AU - Burlet, Arlette
AU - Zannad, Faiez
AU - Meistelman, Claude
AU - Mertes, Paul Michel
AU - Ungureanu-Longrois, Dan
PY - 2001
Y1 - 2001
N2 - Vitamin A and its active metabolite retinoic acid (RA) modulate host-pathogen interactions by interfering with the host immune and inflammatory response including prostaglandin (PG) biosynthesis. The effects of RA on phospholipase A2 (PLA2) and cyclooxygenase (COX) isoforms in vitro are controversial, and few in vivo studies exist. We investigated the in vivo effects of RA on PG biosynthesis in the presence or absence of lipopolysaccharide (LPS) in rats. RA alone [10 mg/(kg·d) for 5 d] increased plasma and liver PG concentrations by increasing COX-1 protein expression (twofold that of control rats). RA acted synergistically with LPS to increase plasma (400-fold) and liver (15-fold) concentrations of prostaglandin E2 (PGE2) and significantly, but to a lesser extent, other PG compared with RA rats, in the absence of major differences in PLA2 expression or activity or COX-1 and COX-2 mRNA or protein expression. The RA+LPS-mediated increase in PGE2 was significantly attenuated (97%) by aminoguanidine (AG), a relatively specific inhibitor of the inducible nitric oxide synthase (NOS2), consistent with the previously reported synergistic effect of RA and LPS on NOS2 expression and activity. In addition, RA and LPS induced the expression of the microsomal isoform of PGE synthase (mPGES). In conclusion, in vivo, RA and LPS increased PG and especially PGE2 concentrations. The PGE2 increase was associated with NOS2-mediated activation of COX and induction of mPGES. These results contribute to the characterization of the effects of vitamin A on the host inflammatory response.
AB - Vitamin A and its active metabolite retinoic acid (RA) modulate host-pathogen interactions by interfering with the host immune and inflammatory response including prostaglandin (PG) biosynthesis. The effects of RA on phospholipase A2 (PLA2) and cyclooxygenase (COX) isoforms in vitro are controversial, and few in vivo studies exist. We investigated the in vivo effects of RA on PG biosynthesis in the presence or absence of lipopolysaccharide (LPS) in rats. RA alone [10 mg/(kg·d) for 5 d] increased plasma and liver PG concentrations by increasing COX-1 protein expression (twofold that of control rats). RA acted synergistically with LPS to increase plasma (400-fold) and liver (15-fold) concentrations of prostaglandin E2 (PGE2) and significantly, but to a lesser extent, other PG compared with RA rats, in the absence of major differences in PLA2 expression or activity or COX-1 and COX-2 mRNA or protein expression. The RA+LPS-mediated increase in PGE2 was significantly attenuated (97%) by aminoguanidine (AG), a relatively specific inhibitor of the inducible nitric oxide synthase (NOS2), consistent with the previously reported synergistic effect of RA and LPS on NOS2 expression and activity. In addition, RA and LPS induced the expression of the microsomal isoform of PGE synthase (mPGES). In conclusion, in vivo, RA and LPS increased PG and especially PGE2 concentrations. The PGE2 increase was associated with NOS2-mediated activation of COX and induction of mPGES. These results contribute to the characterization of the effects of vitamin A on the host inflammatory response.
KW - Nitric oxide
KW - Prostaglandin E synthase
KW - Prostaglandins
KW - Rats
KW - Retinoids
UR - http://www.scopus.com/inward/record.url?scp=0034785270&partnerID=8YFLogxK
U2 - 10.1093/jn/131.10.2628
DO - 10.1093/jn/131.10.2628
M3 - Article
C2 - 11584082
AN - SCOPUS:0034785270
SN - 0022-3166
VL - 131
SP - 2628
EP - 2635
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 10
ER -