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Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells.
Br J Pharmacol 2002; 136(4):613-9BJ

Abstract

The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs). DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL-1beta (3 ng ml(-1)) in a concentration-dependent manner (3 - 30 microM) Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 microM) on the NO production was more obvious at lower concentrations of IL-1beta. IL-1beta induced iNOS protein and mRNA expressions, which were significantly potentiated by DHA. EPA (30 microM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no effect. IL-1beta-induced iNOS protein expression was significantly inhibited by PD 98059 (10 microM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 microM), a selective inhibitor of p38 MAPK activity, had no significant effect, although had a tendency to inhibit slightly. IL-1beta increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA significantly potentiated the IL-1beta-induced phosphorylation of p44/42 MAPK, while it had no significant effect on the phosphorylation of p38 MAPK. These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL-1beta through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. hirafuji@hoku-iryo-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12055140

Citation

Hirafuji, Masahiko, et al. "Docosahexaenoic Acid Potentiates Interleukin-1beta Induction of Nitric Oxide Synthase Through Mechanism Involving P44/42 MAPK Activation in Rat Vascular Smooth Muscle Cells." British Journal of Pharmacology, vol. 136, no. 4, 2002, pp. 613-9.
Hirafuji M, Machida T, Tsunoda M, et al. Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells. Br J Pharmacol. 2002;136(4):613-9.
Hirafuji, M., Machida, T., Tsunoda, M., Miyamoto, A., & Minami, M. (2002). Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells. British Journal of Pharmacology, 136(4), pp. 613-9.
Hirafuji M, et al. Docosahexaenoic Acid Potentiates Interleukin-1beta Induction of Nitric Oxide Synthase Through Mechanism Involving P44/42 MAPK Activation in Rat Vascular Smooth Muscle Cells. Br J Pharmacol. 2002;136(4):613-9. PubMed PMID: 12055140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells. AU - Hirafuji,Masahiko, AU - Machida,Takuji, AU - Tsunoda,Marito, AU - Miyamoto,Atsushi, AU - Minami,Masaru, PY - 2002/6/11/pubmed PY - 2003/1/1/medline PY - 2002/6/11/entrez SP - 613 EP - 9 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 136 IS - 4 N2 - The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs). DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL-1beta (3 ng ml(-1)) in a concentration-dependent manner (3 - 30 microM) Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 microM) on the NO production was more obvious at lower concentrations of IL-1beta. IL-1beta induced iNOS protein and mRNA expressions, which were significantly potentiated by DHA. EPA (30 microM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no effect. IL-1beta-induced iNOS protein expression was significantly inhibited by PD 98059 (10 microM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 microM), a selective inhibitor of p38 MAPK activity, had no significant effect, although had a tendency to inhibit slightly. IL-1beta increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA significantly potentiated the IL-1beta-induced phosphorylation of p44/42 MAPK, while it had no significant effect on the phosphorylation of p38 MAPK. These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL-1beta through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/12055140/Docosahexaenoic_acid_potentiates_interleukin_1beta_induction_of_nitric_oxide_synthase_through_mechanism_involving_p44/42_MAPK_activation_in_rat_vascular_smooth_muscle_cells_ L2 - https://doi.org/10.1038/sj.bjp.0704768 DB - PRIME DP - Unbound Medicine ER -